title: CD8+CD45RA+CCR7+FOXP3+ T cells with immunosuppressive properties: a novel subset of inducible human regulatory T cells.
abstract: CD8 T cells stimulated with a suboptimal dose of anti-CD3 Abs (100 pg/ml) in the presence of IL-15 retain a naive phenotype with expression of CD45RA, CD28, CD27, and CCR7 but acquire new functions and differentiate into immunosuppressive T cells. CD8+CCR7+ regulatory T cells (Tregs) express FOXP3 and prevent CD4 T cells from responding to TCR stimulation and entering the cell cycle. Naive CD4 T cells are more susceptible to inhibition than memory cells. The suppressive activity of CD8+CCR7+ Tregs is not mediated by IL-10, TGF-β, CTLA-4, CCL4, or adenosine and relies on interference with very early steps of the TCR signaling cascade. Specifically, CD8+CCR7+ Tregs prevent TCR-induced phosphorylation of ZAP70 and dampen the rise of intracellular calcium in CD4 T cells. The inducibility of CD8+CCR7+ Tregs is correlated with the age of the individual with PBLs of donors older than 60 y yielding low numbers of FOXP3(low) CD8 Tregs. Loss of CD8+CCR7+ Tregs in the elderly host may be of relevance in the aging immune system as immunosenescence is associated with a state of chronic smoldering inflammation.
authors: Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors: Masakatsu
authors: M
authors: Suzuki
authors: Ann L
authors: AL
authors: Jagger
authors: Christine
authors: C
authors: Konya
authors: Yasuhiro
authors: Y
authors: Shimojima
authors: Sergey
authors: S
authors: Pryshchep
authors: Jörg J
authors: JJ
authors: Goronzy
authors: Cornelia M
authors: CM
authors: Weyand
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology; D016827:CD8 Antigens / Q000096:biosynthesis*; D016923:Cell Death / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D006801:Humans; D007108:Immune Tolerance; D017493:Leukocyte Common Antigens / Q000096:biosynthesis*; D008875:Middle Aged; D061251:Primary Cell Culture; D054400:Receptors, CCR7 / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D016827:CD8 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D054400:Receptors, CCR7; D017493:Leukocyte Common Antigens