Affinage

IL2RB

Interleukin-2 receptor subunit beta · UniProt P14784

Length
551 aa
Mass
61.1 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL-2Rβ (CD122) is the shared β-chain subunit of the interleukin-2 and interleukin-15 receptors that transduces JAK1/STAT5 signals to control lymphocyte homeostasis, effector differentiation, and immune tolerance. Surface abundance of IL-2Rβ is the rate-limiting determinant of IL-2/IL-15 responsiveness: it is regulated post-translationally by ADAM17-mediated ectodomain shedding and FUT8-dependent core fucosylation, and transcriptionally by Runx3 and IL-27 signaling (PMID:38918390, PMID:40753573, PMID:18003603, PMID:41364763). Graded CD122 signal strength specifies distinct cell fates—weak signaling supports CD8+ central-memory T cells while stronger signaling is required for effector-memory differentiation, and precise timing of CD122 expression governs iNKT subset and Treg development (PMID:21984699, PMID:34054809, PMID:21541329). Homozygous hypomorphic IL2RB mutations in humans cause immune dysregulation with defective Treg development, impaired NK cell maturation, and expanded effector CD8+ T cells, establishing IL-2Rβ as essential for human immune tolerance (PMID:31040184, PMID:40570369).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 Medium

    Early expression mapping established that CD122 marks hematopoietic stem cells and the earliest lymphoid progenitors, suggesting a developmental role for IL-2Rβ signaling before mature lymphocyte differentiation.

    Evidence Flow cytometry and in situ mRNA localization on fetal liver and thymic progenitors with functional IL-2 proliferation assays

    PMID:8547641

    Open questions at the time
    • No loss-of-function evidence at the progenitor stage
    • Relative contributions of IL-2 vs. IL-15 signaling through CD122 in progenitors undefined
  2. 2004 High

    The discovery that CD8+CD122+ T cells constitute a naturally occurring regulatory population capable of preventing autoimmune-like disease in CD122-deficient mice established a non-redundant immunosuppressive function for CD122-expressing CD8+ T cells.

    Evidence Adoptive transfer of CD8+CD122+ cells into CD122-knockout neonates; in vitro co-culture suppression assays

    PMID:15520244

    Open questions at the time
    • Mechanism of suppression (soluble vs. contact) was unresolved
    • Antigen specificity of recognition unknown
  3. 2005 High

    Identification of IL-10 as the essential effector cytokine of CD8+CD122+ Tregs resolved the suppressive mechanism, showing it was soluble-factor-mediated rather than TGF-β-dependent.

    Evidence In vitro co-culture with neutralizing anti-IL-10 and anti-TGF-β antibodies; cells from IL-10 knockout mice

    PMID:16301610

    Open questions at the time
    • Whether contact-dependent killing also contributes was not addressed
    • In vivo relevance of IL-10 production in Treg function not fully demonstrated
  4. 2008 High

    Two studies defined the recognition and costimulatory requirements of CD8+CD122+ Tregs: target recognition occurs via conventional MHC class I–αβTCR interaction, and activation requires CD28 costimulation through CD80/CD86, placing these Tregs within classical T cell activation paradigms.

    Evidence MHC-congenic mouse strains with blocking antibodies against MHC I, TCR, CD8, CD28, CD80, CD86; CD28-knockout mice

    PMID:18205792 PMID:18495626

    Open questions at the time
    • Specific antigens recognized by these Tregs remain unidentified
    • Whether CD28 signals directly drive IL-10 transcription or act indirectly was unknown
  5. 2010 High

    PD-1 expression was shown to distinguish regulatory (PD-1+) from memory (PD-1−) cells within the CD8+CD122+ compartment, resolving the heterogeneity of this population and revealing that both CD28 and PD-1 signals cooperate for optimal IL-10 production.

    Evidence PD-1 subset sorting with in vitro suppression assays and in vivo transfer experiments; antibody blockade

    PMID:20548035

    Open questions at the time
    • Developmental origin of PD-1+ vs. PD-1− subsets unclear
    • Whether PD-1 provides a costimulatory or survival signal to Tregs not mechanistically resolved
  6. 2011 High

    Engineered CD122 cytoplasmic-tail mutant mice demonstrated that graded signal strength through IL-2Rβ specifies CD8+ T cell memory fate: weak signaling sustains central-memory cells while stronger signaling is required for effector-memory differentiation independently of Bcl-2 survival.

    Evidence CD122 signaling-domain mutant knockin mice; Bcl-2 transgenic epistasis; OT-I adoptive transfer

    PMID:21984699

    Open questions at the time
    • Which specific STAT5 target genes drive TEM vs. TCM fate not identified
    • Contribution of IL-2 vs. IL-15 to each memory subset in vivo not fully dissected
  7. 2011 Medium

    Continuous IL-15/CD122-driven STAT5 phosphorylation in Foxp3+ thymic Treg precursors was shown to exceed that in other CD4+ thymocytes and to correlate with CD122 rather than CD25 expression, placing CD122 signaling upstream of Treg lineage commitment.

    Evidence Ex vivo intracellular pSTAT5 flow cytometry in neonatal and adult murine thymus; IL-2/IL-15/IL-7 stimulation

    PMID:21541329

    Open questions at the time
    • Causal requirement (not just correlation) of CD122 for Treg thymic selection was not directly tested
    • Whether IL-15 or IL-2 is the dominant ligand in vivo at this stage was unclear
  8. 2016 High

    A second, contact-dependent suppressive mechanism of CD8+CD122+ Tregs was uncovered: Fas/FasL-mediated cytotoxicity kills activated target T cells, operating independently of IL-10 secretion and refining the subset to CD49dlow cells.

    Evidence In vitro and in vivo suppression assays using lpr (Fas-deficient) and gld (FasL-deficient) mutant mice; CD49d fractionation

    PMID:26869716

    Open questions at the time
    • Relative in vivo contribution of IL-10 vs. Fas/FasL pathways not quantified
    • Whether both mechanisms operate simultaneously or in distinct contexts is unknown
  9. 2018 High

    CD122 was identified as the critical receptor enabling costimulation-independent recall of CD8+ memory T cells during allograft rejection, with IL-15R (not IL-2R) signaling through CD122 being the operative pathway—providing a therapeutic rationale for CD122 blockade in transplantation.

    Evidence Mouse and nonhuman primate transplant models with anti-CD122 antibody blockade; genetic dissection of IL-2 vs. IL-15 receptor contributions

    PMID:30222140

    Open questions at the time
    • Precise intracellular signaling differences between IL-2R and IL-15R through CD122 in memory recall not defined
    • Long-term immunological consequences of CD122 blockade not assessed
  10. 2019 High

    A homozygous hypomorphic WSXWS-motif mutation in human IL2RB established the gene as essential for human immune tolerance and NK cell terminal maturation, directly linking reduced CD122 surface expression to diminished STAT5 phosphorylation, Treg deficiency, and CD56bright NK cell expansion.

    Evidence Human patient genetic analysis; flow cytometry; functional IL-2/IL-15 signaling assays

    PMID:31040184

    Open questions at the time
    • Only one family reported initially; broader mutational spectrum unknown
    • Whether gene therapy or cytokine supplementation can rescue the phenotype not tested
  11. 2020 High

    Quantitative receptor-level control was demonstrated: naive CD4+ T cells express ~5-fold less CD122 than CD8+ T cells, and transgenic CD122 overexpression on CD4+ T cells conferred IL-15 responsiveness and lymphopenia-induced homeostatic proliferation, establishing surface CD122 abundance as the rate-limiting factor.

    Evidence Surface receptor quantification; transgenic CD122 overexpression on CD4+ T cells; in vivo lymphopenic proliferation assays

    PMID:32393513

    Open questions at the time
    • What controls the differential CD122 expression between CD4+ and CD8+ lineages at the transcriptional level was not addressed
  12. 2021 Medium

    Precise timing and abundance of CD122 expression were shown to control iNKT cell development: premature expression was detrimental, CD122 was necessary for NKT1 but not NKT2/NKT17 generation, and supraphysiological CD122 paradoxically suppressed NKT1 differentiation—revealing a Goldilocks requirement.

    Evidence Genetic mouse models with altered IL-2Rβ expression timing and abundance; thymic iNKT subset flow cytometry

    PMID:34054809

    Open questions at the time
    • Molecular basis for the biphasic dose-response (too much CD122 being inhibitory) not elucidated
    • Whether IL-2 or IL-15 mediates the NKT1-promoting signal is not resolved
  13. 2024 High

    ADAM17 was identified as the sheddase that cleaves membrane CD122, providing the first post-translational mechanism controlling CD122 surface abundance: T cell-specific ADAM17 deletion increased CD122 levels and enhanced IL-2/IL-15 responsiveness, boosting anti-tumor and anti-pathogen CD8+ T cell immunity.

    Evidence Conditional ADAM17 knockout in T cells; transcriptomic/proteomic analysis; human and mouse CD8+ T cell IL-2/IL-15 stimulation; CAR-T tumor models

    PMID:38918390

    Open questions at the time
    • Specific cleavage site on CD122 not mapped
    • Whether soluble cleaved CD122 ectodomain has biological activity is unknown
    • Regulation of ADAM17 activity toward CD122 during immune responses not characterized
  14. 2025 High

    Core fucosylation by FUT8 was identified as essential for CD122 surface stability and NK cell homeostasis: NK-specific Fut8 deletion caused severe NK lymphopenia with reduced CD122 surface expression and impaired IL-15-driven proliferation, tumor immunity, and antiviral defense.

    Evidence Genome-wide CRISPR screen in human NK cells validated by conditional NK-specific Fut8 knockout mouse; flow cytometry; in vivo functional assays

    PMID:40753573

    Open questions at the time
    • Specific fucosylation sites on CD122 not identified
    • Whether FUT8 affects CD122 folding, trafficking, or protection from shedding is unclear
  15. 2025 Medium

    IL-27 was placed upstream of CD122 in Treg homeostasis: IL-27 promotes CD122 expression on Tregs, and IL-27R-deficient Tregs were competitively disadvantaged and eroded with aging—phenocopied by CD122 blockade—establishing a cytokine–receptor cascade maintaining long-term Treg fitness.

    Evidence Mixed bone marrow chimeras with IL-27R-sufficient and -deficient Tregs; aging experiments; CD122 blockade; in vivo and in vitro IL-27 stimulation

    PMID:41364763

    Open questions at the time
    • Whether IL-27 directly drives IL2RB transcription or acts indirectly is not resolved
    • Relevance of IL-27/CD122 axis in human Treg biology not tested
  16. 2025 High

    A hypomorphic IL2RB knockin mouse fully recapitulated human IL-2Rβ deficiency and demonstrated that Tregs and CD8+ T cells have distinct IL-2/IL-15 signaling thresholds through CD122, with WT Treg transfer alone being sufficient to normalize the T cell compartment—establishing a potential therapeutic principle.

    Evidence Homologous knockin mouse; mixed bone marrow chimeras; neonatal WT Treg adoptive transfer; STAT5 phosphorylation assays

    PMID:40570369

    Open questions at the time
    • Whether the signaling threshold difference is cell-intrinsic to CD122 expression level or involves co-receptor differences is not fully resolved
    • Long-term outcomes of Treg transfer therapy not assessed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the precise structural basis of the ADAM17 cleavage site and FUT8 fucosylation sites on CD122, whether soluble cleaved CD122 ectodomain has decoy-receptor activity, and the transcription factor network that establishes differential CD122 expression between CD4+ and CD8+ T cell lineages.
  • Structural mapping of ADAM17 cleavage site and FUT8-modified residues on CD122
  • Function of soluble CD122 ectodomain
  • Complete transcriptional regulatory network for IL2RB across lineages

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5
Localization
GO:0005886 plasma membrane 5
Pathway
R-HSA-168256 Immune System 8
Partners
ADAM17FUT8IL15RAIL2RAIL2RGJAK1STAT5
Complex memberships
IL-15 receptor complex (IL-15Rα/IL-2Rβ/γc)IL-2 receptor complex (IL-2Rα/IL-2Rβ/γc)

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 CD8+CD122+ T cells constitute a naturally occurring regulatory T cell population that can directly suppress both CD8+ and CD4+ T cell activity in vivo and in vitro, with transfer of these cells into CD122-deficient neonates preventing development of abnormal activated T cells. Adoptive cell transfer into CD122-deficient mice; in vitro co-culture suppression assays The Journal of experimental medicine High 15520244
2005 CD8+CD122+ regulatory T cells suppress IFN-γ production and proliferation of CD8+ target cells primarily through secretion of IL-10; blockade of IL-10 (but not TGF-β) abrogated suppression, and CD8+CD122+ cells from IL-10-deficient mice lacked regulatory activity. In vitro co-culture with neutralizing antibodies; conditioned medium depletion experiments; cells from IL-10 knockout mice Journal of immunology High 16301610
2008 CD8+CD122+ regulatory T cells recognize activated target T cells via conventional MHC class I–αβTCR interaction (involving H-2K, H-2D, αβTCR, and CD8, but not I-A or Qa-1), and this recognition activates them to produce IL-10 and suppress IFN-γ production. MHC-congenic mouse strains; blocking antibodies against cell-surface molecules; in vitro co-culture system International immunology High 18495626
2008 CD8+CD122+ regulatory T cell activation and IL-10 production requires CD80/CD86–CD28 co-stimulatory signaling; cells from CD28-knockout mice lacked regulatory activity, and blocking CD80, CD86, or CD28 (but not CTLA-4, ICOS, or PD-1) abrogated suppression. Blocking antibodies; CD28-/- knockout mice; in vitro co-culture assays Immunology High 18205792
2010 PD-1 expression distinguishes regulatory (PD-1+) from memory (PD-1−) CD8+CD122+ T cells; only the PD-1+ subset suppressed T cell responses via IL-10, while PD-1− cells were antigen-specific memory T cells. Both CD28 and PD-1 co-stimulatory signals are required for optimal IL-10 production by the Treg subset. In vitro suppression assays; in vivo transfer experiments; PD-1 subset sorting; antibody blockade of co-stimulatory molecules Journal of immunology High 20548035
2016 CD8+CD122+CD49dlow regulatory T cells kill activated T cells via Fas/FasL (CD95/CD178)-mediated cytotoxicity; cells from lpr (Fas-deficient) mice were resistant to Treg-mediated suppression, and gld (FasL-deficient) Tregs could not regulate wild-type T cells. IL-10 was not required for this killing mechanism but was separable from it. In vitro and in vivo regulation assays using lpr and gld mutant mice; CD49d subset fractionation Proceedings of the National Academy of Sciences of the United States of America High 26869716
2019 A homozygous hypomorphic human IL2RB mutation in the WSXWS motif results in diminished IL-2Rβ surface expression, dysregulated IL-2/IL-15 signaling (reduced STAT5 phosphorylation), reduced regulatory T cells, expansion of CD56bright NK cells, and absence of terminally differentiated NK cells — establishing IL-2Rβ as essential for human immune tolerance and NK cell maturation. Human patient genetic and immunological analysis; flow cytometry; functional IL-2/IL-15 signaling assays The Journal of experimental medicine High 31040184
2011 Weak CD122-dependent signaling supports development and survival of CD8+ T central-memory (TCM) cells but not T effector-memory (TEM) cells; stronger CD122 signals are required for TEM development independently of Bcl-2 survival signals. Proximal IL-2 signaling sustains p-STAT5 and p-S6 longer than IL-15 due to limited IL-15Rα expression. Cytoplasmic-tail CD122 mutant mouse models; transgenic Bcl-2 rescue; OT-I adoptive transfer; in vivo primary and memory CD8+ T cell response analysis Journal of immunology High 21984699
2018 Costimulation-independent CD8+ memory T cell alloreactivity is mediated through CD122 (IL-2/IL-15Rβ) signaling; combined costimulatory and CD122 blockade improved transplant survival in mice and nonhuman primates. Signaling through CD122 as part of the high-affinity IL-15R (but not the high-affinity IL-2R) was critical for costimulation-independent memory CD8+ T cell recall. Mouse and nonhuman primate transplant models; antibody blockade of CD122; genetic dissection of IL-2 vs. IL-15 receptor contributions The Journal of clinical investigation High 30222140
2001 Fibroblast-like synoviocytes (FLS) express functional IL-2Rβ (CD122) and IL-2Rγ (CD132) but not CD25, and IL-2 stimulation through CD122 induces MCP-1 production in FLS; this was blocked by anti-CD122 antibody, and IL-2 treatment caused increased tyrosine phosphorylation in FLS. Western blot; ELISA; flow cytometry; neutralizing antibody blockade; tyrosine phosphorylation assay Journal of immunology Medium 11238664
2007 Runx3 transcription factor binds to the promoter region of the CD122 (IL2RB) gene and regulates its expression; introduction of a dominant-negative Runx form into hematopoietic stem cells in NK-cell-inducing culture decreased CD122 expression, and transgenic dominant-negative Runx expression in NK cells decreased Ly49 family maturation markers. Promoter binding assay; dominant-negative Runx transgenic mice; in vitro NK differentiation cultures; RT-PCR International immunology Medium 18003603
2011 IL-15/CD122 signaling drives continuous STAT5 phosphorylation in regulatory T cell precursors during thymic selection; pSTAT5 was higher in Foxp3+ Tregs than other CD4+ thymocytes, correlated better with Foxp3 and CD122 than with CD25, and disappeared rapidly without in vivo cytokine signals. Ex vivo pSTAT5 flow cytometry in neonatal and adult murine thymus; in vitro IL-2/IL-15/IL-7 stimulation; neonatal thymus analysis PloS one Medium 21541329
2020 The abundance of IL-2Rβ (CD122) on the cell surface constrains lymphopenia-induced homeostatic proliferation (LIP) of naive CD4+ T cells; naive CD4+ T cells express ~5-fold less CD122 than CD8+ T cells, and forced transgenic expression of CD122 on CD4+ T cells conferred IL-15 responsiveness and robust LIP. Surface IL-2Rβ quantification by flow cytometry; transgenic CD122 overexpression on CD4+ T cells; lymphopenic in vivo LIP assays Journal of immunology High 32393513
2024 ADAM17 (a disintegrin and metalloprotease) cleaves membrane CD122 via ectodomain shedding, thereby restraining CD8+ T cell effector differentiation; T cell-specific deletion of ADAM17 increased CD122 surface expression and enhanced IL-2 and IL-15 responsiveness in both mouse and human CD8+ T cells, promoting anti-tumor and anti-pathogen immunity. T cell-specific ADAM17 conditional knockout mice; transcriptomic and proteomic analysis; IL-2/IL-15 stimulation assays; human CD8+ T cell experiments; CAR-T tumor models Signal transduction and targeted therapy High 38918390
2025 Core fucosylation of IL-2Rβ (CD122) by fucosyltransferase 8 (FUT8) is required for NK cell homeostasis; loss of FUT8 in NK cells (Fut8fl/fl Ncr1cre/+) caused severe NK lymphopenia with reduced CD122 surface expression, impaired IL-15-driven homeostatic proliferation, reduced cytotoxicity, and impaired tumor and viral immunity. Genome-wide CRISPR screen in human NK cells; conditional NK-specific Fut8 knockout mouse; flow cytometry; in vivo NK homeostatic proliferation; tumor and viral immunity assays Cell reports High 40753573
1996 CD122 is expressed on Sca1+Lin− hematopoietic stem cells in fetal liver and on intrathymic Sca1+ T cell progenitors, and its expression marks the earliest B220+ prepro-B cells (fraction A) that proliferate in response to IL-2 but not IL-15, suggesting a role for CD122/IL-2 signaling in early lymphocyte development. Flow cytometry; in situ mRNA localization; functional IL-2 proliferation assay of sorted progenitors Blood Medium 8547641
2021 The timing and abundance of IL-2Rβ (CD122) expression control iNKT cell development and NKT1 subset differentiation in the thymus; premature CD122 expression on immature iNKT cells was detrimental to their development, while CD122 is necessary for NKT1 (but not NKT2 or NKT17) generation, and increased CD122 abundance paradoxically suppressed NKT1 differentiation. Genetic mouse models with altered IL-2Rβ expression timing and abundance; thymic iNKT subset analysis by flow cytometry Frontiers in immunology Medium 34054809
2020 Nicotine increases miR-629-5p expression in CD8+ T cells, which targets IL2RB mRNA and reduces IL-2Rβ protein levels, consequently suppressing granzyme B expression and exhausting CD8+ T cell cytotoxic function against tumor cells. RNAseq; small RNAseq; miR-629-5p mimic transfection; IL2RB knockdown; luciferase/target validation; humanized tumor xenograft model Cancer immunology, immunotherapy Medium 33146402
2025 IL-27 promotes Treg cell expression of CD122 and improves Treg responsiveness to IL-2/IL-15; IL-27R-deficient Tregs were at a competitive disadvantage and were preferentially eroded with aging, associated with reduced CD122 expression; blockade of CD122 led to similar loss of Treg cells, placing IL-27 upstream of CD122 in Treg homeostasis. Mixed bone marrow chimeras with IL-27R-sufficient and -deficient Tregs; aging experiments; CD122 blockade; in vitro and in vivo IL-27 stimulation Proceedings of the National Academy of Sciences of the United States of America Medium 41364763
2025 A hypomorphic IL2RB knockin mouse recapitulates human IL-2Rβ deficiency: decreased IL-2Rβ surface expression, impaired IL-2/IL-15-dependent STAT5 signaling, elevated serum IL-2/IL-15, expanded effector memory CD8+ T cells, and severely reduced Tregs. Mixed bone marrow chimeras and WT Treg neonatal transfers demonstrate that Tregs and CD8+ T cells have distinct IL-2/15 signaling thresholds, with WT Treg transfer achieving near-complete restoration of T cell distribution and STAT5 signaling. Homologous knockin mouse; mixed bone marrow chimeras; WT Treg adoptive transfer; flow cytometry; STAT5 phosphorylation assays Cell reports High 40570369
2024 IL2RB activates the JAK1/STAT5 signaling pathway in esophageal squamous cell carcinoma cells; IL2RB knockdown inhibited tumor cell proliferation, migration, invasion, EMT, and induced CD8+ T cell depletion in the tumor microenvironment. Gain- and loss-of-function experiments; in vivo tumor models; western blotting for JAK1/STAT5 pathway Annals of clinical and laboratory science Medium 40750242
2020 IL-2Rβ (CD122)-selective IL-2 complexes reduce Treg-mediated immunosuppression by inhibiting high-affinity IL-2R signaling in Tregs while simultaneously stimulating effector T cells through CD122; this preferential CD122 targeting induces a fragile Treg phenotype with reduced suppressive function specifically within the tumor microenvironment. Orthotopic mouse tumor models; antibody-mediated cell depletions; flow cytometry; in vivo IL-2 complex treatment Cancer research Medium 32948605
1994 Activation of PKC β1 isozyme induces expression of both IL-2Rα (CD25) and IL-2Rβ (CD122) on human peripheral blood T and B lymphocytes alongside IL-2 production and DNA synthesis, implicating PKC β1 in upstream regulation of CD122 expression during lymphocyte activation. PKC isozyme-selective agonist (dPPA) treatment; flow cytometry for CD122/CD25 surface expression; PKC translocation assay; DNA synthesis measurement Journal of clinical immunology Low 7929699
2024 miR-7704 inhibits ovarian cancer cell proliferation and promotes cisplatin sensitivity by targeting IL2RB to inactivate AKT signaling; IL2RB overexpression reversed miR-7704-mediated cisplatin sensitization, establishing a miR-7704/IL2RB/AKT regulatory feedback loop. miRNA mimic/inhibitor transfection; IL2RB knockdown and overexpression; AKT pathway western blotting; in vitro and in vivo tumor models Experimental cell research Medium 38565343
2020 IL2RB is a target gene of the Wilms' tumor 1 (WT1) transcription factor; WT1 silencing by lentiviral siRNA in K562 myeloid leukemia cells suppressed IL2RB (and IL-2, IL-2RG) mRNA expression alongside induction of apoptosis and growth inhibition. Lentiviral siRNA knockdown of WT1; qPCR for target gene expression; apoptosis and cell cycle assays BioMed research international Low 33110919

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Essential roles of CD8+CD122+ regulatory T cells in the maintenance of T cell homeostasis. The Journal of experimental medicine 232 15520244
2005 Cutting edge: CD8+CD122+ regulatory T cells produce IL-10 to suppress IFN-gamma production and proliferation of CD8+ T cells. Journal of immunology (Baltimore, Md. : 1950) 223 16301610
2008 Essential role of CD8+CD122+ regulatory T cells in the recovery from experimental autoimmune encephalomyelitis. Journal of immunology (Baltimore, Md. : 1950) 125 18178821
2005 Human short-term repopulating stem cells are efficiently detected following intrafemoral transplantation into NOD/SCID recipients depleted of CD122+ cells. Blood 117 15878972
2010 Cutting edge: programmed death-1 defines CD8+CD122+ T cells as regulatory versus memory T cells. Journal of immunology (Baltimore, Md. : 1950) 108 20548035
2010 CD8+CD122+ regulatory T cells (Tregs) and CD4+ Tregs cooperatively prevent and cure CD4+ cell-induced colitis. Journal of immunology (Baltimore, Md. : 1950) 82 21098236
2013 Natural CD8+CD122+ T cells are more potent in suppression of allograft rejection than CD4+CD25+ regulatory T cells. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 79 24219162
2008 CD8+CD122+ regulatory T cells recognize activated T cells via conventional MHC class I-alphabetaTCR interaction and become IL-10-producing active regulatory cells. International immunology 78 18495626
2009 Human CD8+CXCR3+ T cells have the same function as murine CD8+CD122+ Treg. European journal of immunology 77 19609979
2019 A novel human IL2RB mutation results in T and NK cell-driven immune dysregulation. The Journal of experimental medicine 73 31040184
2007 Runx proteins are involved in regulation of CD122, Ly49 family and IFN-gamma expression during NK cell differentiation. International immunology 71 18003603
2016 CD8+CD122+CD49dlow regulatory T cells maintain T-cell homeostasis by killing activated T cells via Fas/FasL-mediated cytotoxicity. Proceedings of the National Academy of Sciences of the United States of America 67 26869716
2011 Antitumor immunity produced by the liver Kupffer cells, NK cells, NKT cells, and CD8 CD122 T cells. Clinical & developmental immunology 62 22190974
2007 CD8+CD122+ T cells, a newly identified regulatory T subset, negatively regulate Graves' hyperthyroidism in a murine model. Endocrinology 62 17823258
2011 The basis of distinctive IL-2- and IL-15-dependent signaling: weak CD122-dependent signaling favors CD8+ T central-memory cell survival but not T effector-memory cell development. Journal of immunology (Baltimore, Md. : 1950) 58 21984699
2017 IL-1β and IL-23 Promote Extrathymic Commitment of CD27+CD122- γδ T Cells to γδT17 Cells. Journal of immunology (Baltimore, Md. : 1950) 55 28855314
2015 CD8(+)CD122(+) T-Cells: A Newly Emerging Regulator with Central Memory Cell Phenotypes. Frontiers in immunology 51 26539191
2014 Regulatory CD8(+)CD122 (+) T-cells predominate in CNS after treatment of experimental stroke in male mice with IL-10-secreting B-cells. Metabolic brain disease 47 25537181
2018 CD122 signaling in CD8+ memory T cells drives costimulation-independent rejection. The Journal of clinical investigation 46 30222140
2010 Polymorphisms in the IL2, IL2RA and IL2RB genes in multiple sclerosis risk. European journal of human genetics : EJHG 45 20179739
2014 A naturally occurring CD8(+)CD122(+) T-cell subset as a memory-like Treg family. Cellular & molecular immunology 44 24793406
2003 Regulation of human short-term repopulating cell (STRC) engraftment in NOD/SCID mice by host CD122+ cells. Experimental hematology 44 12829032
2014 IL-15-dependent CD8+ CD122+ T cells ameliorate experimental autoimmune encephalomyelitis by modulating IL-17 production by CD4+ T cells. European journal of immunology 39 25142300
2000 Mouse CD8+ CD122+ T cells with intermediate TCR increasing with age provide a source of early IFN-gamma production. Journal of immunology (Baltimore, Md. : 1950) 38 10820240
2017 A New Immunosuppressive Molecule Emodin Induces both CD4+FoxP3+ and CD8+CD122+ Regulatory T Cells and Suppresses Murine Allograft Rejection. Frontiers in immunology 33 29167674
2006 Age-related CD8+ T cell clonal expansions express elevated levels of CD122 and CD127 and display defects in perceiving homeostatic signals. Journal of immunology (Baltimore, Md. : 1950) 33 16920913
2020 CD122-Selective IL2 Complexes Reduce Immunosuppression, Promote Treg Fragility, and Sensitize Tumor Response to PD-L1 Blockade. Cancer research 31 32948605
2004 Essential role of bystander cytotoxic CD122+CD8+ T cells for the antitumor immunity induced in the liver of mice by alpha-galactosylceramide. Journal of immunology (Baltimore, Md. : 1950) 31 15153469
2020 Chronic shift-lag promotes NK cell ageing and impairs immunosurveillance in mice by decreasing the expression of CD122. Journal of cellular and molecular medicine 30 33185980
2010 CD122+CD8+ Treg suppress vaccine-induced antitumor immune responses in lymphodepleted mice. European journal of immunology 30 20186876
2008 Importance of CD80/CD86-CD28 interactions in the recognition of target cells by CD8+CD122+ regulatory T cells. Immunology 29 18205792
2001 Functional IL-2 receptor beta (CD122) and gamma (CD132) chains are expressed by fibroblast-like synoviocytes: activation by IL-2 stimulates monocyte chemoattractant protein-1 production. Journal of immunology (Baltimore, Md. : 1950) 29 11238664
2017 Suppression of allograft rejection by CD8+CD122+PD-1+ Tregs is dictated by their Fas ligand-initiated killing of effector T cells versus Fas-mediated own apoptosis. Oncotarget 24 28445940
2022 Combining bempegaldesleukin (CD122-preferential IL-2 pathway agonist) and NKTR-262 (TLR7/8 agonist) improves systemic antitumor CD8+ T cell cytotoxicity over BEMPEG+RT. Journal for immunotherapy of cancer 23 35444059
1996 Regulated expression and function of CD122 (interleukin-2/interleukin-15R-beta) during lymphoid development. Blood 23 8547641
2018 IL-10 producing CD8+ CD122+ PD-1+ regulatory T cells are expanded by dendritic cells silenced for Allograft Inflammatory Factor-1. Journal of leukocyte biology 22 30512224
2023 Expansion of circulating stem-like CD8+ T cells by adding CD122-directed IL-2 complexes to radiation and anti-PD1 therapies in mice. Nature communications 20 37045833
2021 CD122-directed interleukin-2 treatment mechanisms in bladder cancer differ from αPD-L1 and include tissue-selective γδ T cell activation. Journal for immunotherapy of cancer 20 33849925
2019 CD8+CD122+PD-1+ Tregs Synergize With Costimulatory Blockade of CD40/CD154, but Not B7/CD28, to Prolong Murine Allograft Survival. Frontiers in immunology 20 30863408
2019 Effect of IL2RA and IL2RB gene polymorphisms on lung cancer risk. International immunopharmacology 20 31279323
2013 The Rag2⁻Il2rb⁻Dmd⁻ mouse: a novel dystrophic and immunodeficient model to assess innovating therapeutic strategies for muscular dystrophies. Molecular therapy : the journal of the American Society of Gene Therapy 20 23975040
2021 Evolutionary genetic algorithm identifies IL2RB as a potential predictive biomarker for immune-checkpoint therapy in colorectal cancer. NAR genomics and bioinformatics 19 33928242
2019 IL2RB maintains immune harmony. The Journal of experimental medicine 18 31068380
2017 c-REL and IκBNS Govern Common and Independent Steps of Regulatory T Cell Development from Novel CD122-Expressing Pre-Precursors. Journal of immunology (Baltimore, Md. : 1950) 16 28652399
2014 CD8+ CD122+ PD-1- effector cells promote the development of diabetes in NOD mice. Journal of leukocyte biology 16 25387835
2013 Association of IL-2RA and IL-2RB genes with erosive status in early rheumatoid arthritis patients (ESPOIR and RMP cohorts). Joint bone spine 16 24200909
2019 Association between ADRB2, IL33, and IL2RB gene polymorphisms and lung cancer risk in a Chinese Han population. International immunopharmacology 15 31685439
2014 Genetic polymorphisms in IL-2, IL-10, TGF-β1, and IL-2RB and acute rejection in renal transplant patients. Clinical transplantation 15 24579958
2016 CXCR3 May Help Regulate the Inflammatory Response in Acute Lung Injury via a Pathway Modulated by IL-10 Secreted by CD8 + CD122+ Regulatory T Cells. Inflammation 14 26475448
2020 Nicotine exhausts CD8+ T cells against tumor cells through increasing miR-629-5p to repress IL2RB-mediated granzyme B expression. Cancer immunology, immunotherapy : CII 13 33146402
2024 Astragalus polysaccharide enhances antitumoral effects of chimeric antigen receptor- engineered (CAR) T cells by increasing CD122+CXCR3+PD-1- memory T cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 12 39243425
2021 Human CD8 T-stem cell memory subsets phenotypic and functional characterization are defined by expression of CD122 or CXCR3. European journal of immunology 12 33844287
2020 The Abundance and Availability of Cytokine Receptor IL-2Rβ (CD122) Constrain the Lymphopenia-Induced Homeostatic Proliferation of Naive CD4 T Cells. Journal of immunology (Baltimore, Md. : 1950) 12 32393513
2019 Single nucleotide polymorphisms of the genes IL-2, IL-2RB, and JAK3 in patients with cutaneous leishmaniasis caused by Leishmania (V.) guyanensis in Manaus, Amazonas, Brazil. PloS one 12 31393896
2017 Chinese medicine Ginseng and Astragalus granules ameliorate autoimmune diabetes by upregulating both CD4+FoxP3+ and CD8+CD122+PD1+ regulatory T cells. Oncotarget 12 28947964
2017 Targeting of CD122 enhances antitumor immunity by altering the tumor immune environment. Oncotarget 12 29312597
2012 Efficient xenoengraftment in severe immunodeficient NOD/Shi-scid IL2rγnull mice is attributed to a lack of CD11c+B220+CD122+ cells. Journal of immunology (Baltimore, Md. : 1950) 12 23018460
2011 Impact of IL2 and IL2RB genetic polymorphisms in kidney transplantation. Transplantation proceedings 12 21839273
2024 Targeting a disintegrin and metalloprotease (ADAM) 17-CD122 axis enhances CD8+ T cell effector differentiation and anti-tumor immunity. Signal transduction and targeted therapy 11 38918390
2024 CXCL9, IL2RB, and SPP1, potential diagnostic biomarkers in the co-morbidity pattern of atherosclerosis and non-alcoholic steatohepatitis. Scientific reports 11 39013959
2021 Downregulation of miR-497-5p Improves Sepsis-Induced Acute Lung Injury by Targeting IL2RB. BioMed research international 11 33954185
2018 Herbal Components of a Novel Formula PSORI-CM02 Interdependently Suppress Allograft Rejection and Induce CD8+CD122+PD-1+ Regulatory T Cells. Frontiers in pharmacology 11 29483872
2013 CD8+ CD122+ regulatory T cells contain clonally expanded cells with identical CDR3 sequences of the T-cell receptor β-chain. Immunology 11 23317140
1997 No evidence for a schizophrenia susceptibility gene in the vicinity of IL2RB on chromosome 22. American journal of medical genetics 11 9259369
2023 Combination of cancer vaccine with CD122-biased IL-2/anti-IL-2 Ab complex shapes the stem-like effector NK and CD8+ T cells against tumor. Journal for immunotherapy of cancer 10 37400134
2023 Exosomes containing miR-1469 regulate natural killer cells by targeting CD122 in non-segmental vitiligo. Journal of dermatological science 10 38307771
1994 12-Deoxyphorbol-13-O-phenylacetate 20 acetate [an agonist of protein kinase C beta 1 (PKC beta 1)] induces DNA synthesis, interleukin-2 (IL-2) production, IL-2 receptor alpha-chain (CD25) and beta-chain (CD122) expression, and translocation of PKC beta isozyme in human peripheral blood lymphocytes: evidence for a role of PKC beta 1 in human T cell activation. Journal of clinical immunology 10 7929699
2021 Role of IL-9, IL-2RA, and IL-2RB genetic polymorphisms in coronary heart disease. Herz 9 33651164
2021 TREM2 promotes natural killer cell development in CD3-CD122+NK1.1+ pNK cells. BMC immunology 9 33980160
2018 Decreased CD122 on CD56dim NK associated with its impairment in asymptomatic chronic HBV carriers with high levels of HBV DNA, HBsAg and HBeAg. Life sciences 9 29307521
2018 Association of genetic variations in PTPN2 and CD122 with ocular Behcet's disease. The British journal of ophthalmology 9 29502070
2011 Continuous activation of the CD122/STAT-5 signaling pathway during selection of antigen-specific regulatory T cells in the murine thymus. PloS one 9 21541329
2010 Roles of CD122+ cells in resistance against Neospora caninum infection in a murine model. The Journal of veterinary medical science 9 20460838
2023 Anti-CD122 antibody restores specific CD8+ T cell response in nonalcoholic steatohepatitis and prevents hepatocellular carcinoma growth. Oncoimmunology 8 36891258
2022 Upregulated Expression of IL2RB Causes Disorder of Immune Microenvironment in Patients with Kawasaki Disease. BioMed research international 8 35924269
2017 Changes and clinical significance of CD8+CD122+ T cells in the peripheral blood of patients with ankylosing spondylitis. Clinical rheumatology 8 29110110
2024 CSF1R blockade slows progression of cerebral hemorrhage by reducing microglial proliferation and increasing infiltration of CD8 + CD122+ T cells into the brain. International immunopharmacology 7 38636374
2023 IL2RB affects Th1/Th2 and Th17 responses of peripheral blood mononuclear cells from septic patients. Allergologia et immunopathologia 7 37169553
2021 Impact of genetic variants in IL-2RA and IL-2RB on breast cancer risk in Chinese Han women. Biochemical genetics 7 33507447
2019 Genetic analysis of the relation between IL2RA/IL2RB and rheumatoid arthritis risk. Molecular genetics & genomic medicine 7 31134763
2018 Association of the TNF-α, IL-2, and IL-2RB gene variants with susceptibility to psoriasis in a Turkish cohort. Central-European journal of immunology 7 29736146
2025 Targeting the IL-15/CD122 signaling pathway: reversing TRM cell-mediated immune memory in vitiligo. Frontiers in immunology 6 40791580
2021 The Timing and Abundance of IL-2Rβ (CD122) Expression Control Thymic iNKT Cell Generation and NKT1 Subset Differentiation. Frontiers in immunology 6 34054809
2021 CD122-targeted interleukin-2 and αPD-L1 treat bladder cancer and melanoma via distinct mechanisms, including CD122-driven natural killer cell maturation. Oncoimmunology 5 34858732
2024 A miRNA-7704/IL2RB/AKT feedback loop regulates tumorigenesis and chemoresistance in ovarian cancer. Experimental cell research 4 38565343
2024 Human serum albumin promotes interactions between HSA-IL-2 fusion protein and CD122 for enhancing immunotherapy. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 4 39522264
2024 Human placental mesenchymal stromal cells promote the formation of CD8+CD122+PD-1+Tregs via CD73/Foxo1 to alleviate liver injury in graft-versus-host disease mice. International immunopharmacology 3 38968861
2020 CD122-targetted IL-2 signals cause acute and selective apoptosis of B cells in Peyer's Patches. Scientific reports 3 32728053
2020 Novel WT1 Target Genes: IL-2, IL-2RB, and IL-2RG Discovered during WT1 Silencing Using Lentiviral-Based RNAi in Myeloid Leukemia Cells. BioMed research international 3 33110919
2016 Donor-antigen Inoculation in the Testis Promotes Skin Allograft Acceptance Induced by Conventional Costimulatory Blockade via Induction of CD8 + CD122+ and CD4 + CD25+ Regulatory T Cells. Transplantation 3 26569069
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2020 Corrigendum: A New Immunosuppressive Molecule Emodin Induces both CD4+FoxP3+ and CD8+CD122+ Regulatory T Cells and Suppresses Murine Allograft Rejection. Frontiers in immunology 2 32765495
2025 A dual-mode nanoplatform based on Cu2O@Au-Pt nanoenzyme and CHA-HCR DNA framework circuit for sensitive detection of CD122 and CD17. International journal of biological macromolecules 1 40185434
2025 IL2RB Remodels the Immune Microenvironment and Promotes the Progression of Esophageal Squamous Cell Carcinoma. Annals of clinical and laboratory science 1 40750242
2025 Core fucosylation of IL-2RB is required for natural killer cell homeostasis. Cell reports 1 40753573
2024 CD122 is an activation marker ensuring proper proliferation of T cells in teleost. Fish & shellfish immunology 1 39153581
2025 A hypomorphic Il2rb mutant mouse model recapitulates and reveals mechanisms of human T cell immune dysregulation in IL-2Rβ deficiency. Cell reports 0 40570369
2025 IL-27 promotes Treg cell expression of CD122 and fitness at homeostasis. Proceedings of the National Academy of Sciences of the United States of America 0 41364763
2023 Blockade of CD122 on memory T cells in the skin suppresses sclerodermatous graft-versus-host disease. Journal of dermatological science 0 36966029