Cytokine-induced IL-10-secreting CD8 T cells represent a phenotypically distinct suppressor T-cell lineage
Cytokine-induced IL-10-secreting CD8 T cells represent a phenotypically distinct suppressor T-cell lineage
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DOI：
10.1182/blood-2005-10-3994
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发表时间：
2006-06-01
期刊：
影响因子：
20.3
通讯作者：
Leggat, JA
中科院分区：
文献类型：
--
作者：
Noble, A;Giorgini, A;Leggat, JA
调节性T细胞（Tcells）群体控制由自身或外源抗原诱导的自身免疫和过敏性免疫病理学。几种类型的CD 4（+）MHC II类限制性Treg群体已被表征，但CD 8（+）MHC I类限制性Treg群体的生物学尚不清楚。我们在此表明，CD 8（+）T细胞在IL-4和IL-12存在下快速生成，产生IL-10，并表现出独特的细胞表面表型，共表达活化和幼稚细胞相关标志物。它们在体内阻断初始或效应T细胞的活化并抑制IgG/IgE抗体应答和移植物抗宿主病。抑制依赖于细胞接触，并通过拮抗T细胞受体（TCR）信号的直接T细胞-T细胞相互作用介导。这些数据建立了CD 8 T细胞抑制效应子亚群的存在，其在表型和功能上与T细胞毒性1（Tc 1）和Tc 2细胞不同。这种CD 8 T细胞的产生具有用于CD 4或CD 8 T细胞介导的疾病的基于细胞的治疗的潜力。
Populations of regulatory T cells (Tregs) control autoimmune and allergic immunopathology induced by self or foreign antigens. Several types of CD4(+) MHC class II-restricted Treg populations have been characterized, but the biology of CD8(+), MHC class I-restricted Tregs is less understood. We show here that CD8(+) Tregs are rapidly generated in the presence of IL-4 and IL-12, produce IL-10, and exhibit a unique cell-surface phenotype with coexpression of activation and naive cell-associated markers. They block activation of naive or effector T cells and suppress IgG/IgE antibody responses and graft-versus-host disease in vivo. Suppression is dependent on cell contact and mediated by direct T-cell-T-cell interaction that antagonizes T-cell-receptor (TCR) signals. The data establish the existence of a CD8 T-cell suppressor effector subset distinct in both phenotype and function from T cytotoxic 1 (Tc1) and Tc2 cells. Production of such CD8 Tregs has potential for cell-based therapy of CD4 or CD8 T-cell-mediated disease.