Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
J Immunol. 2012 Sep 1;189(5):2118-30. doi: 10.4049/jimmunol.1200122. Epub 2012 Jul 20.
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.
在 IL-15 的存在下，用亚最优剂量的抗 CD3 Ab（100pg/ml）刺激 CD8 T 细胞，保留幼稚表型，表达 CD45RA、CD28、CD27 和 CCR7，但获得新功能并分化为免疫抑制性 T 细胞。CD8+CCR7+调节性 T 细胞（Tregs）表达 FOXP3，防止 CD4 T 细胞对 TCR 刺激做出反应并进入细胞周期。幼稚 CD4 T 细胞比记忆细胞更容易受到抑制。CD8+CCR7+Tregs 的抑制活性不是由 IL-10、TGF-β、CTLA-4、CCL4 或腺苷介导的，而是依赖于干扰 TCR 信号级联的早期步骤。具体来说，CD8+CCR7+Tregs 可防止 TCR 诱导的 ZAP70 磷酸化，并抑制 CD4 T 细胞内钙离子的上升。CD8+CCR7+Tregs 的诱导能力与个体的年龄相关，供体的 PBL 年龄大于 60 岁，导致 FOXP3（低）CD8 Tregs 数量较少。老年宿主中 CD8+CCR7+Tregs 的丧失在衰老的免疫系统中可能具有相关性，因为免疫衰老与慢性潜伏性炎症状态相关。
