CD8+CD122+ regulatory T cells recognize activated T cells via conventional MHC class I-αβTCR interaction and become IL-10-producing active regulatory cells
CD8+CD122+ regulatory T cells recognize activated T cells via conventional MHC class I-αβTCR interaction and become IL-10-producing active regulatory cells
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DOI：
10.1093/intimm/dxn052
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发表时间：
2008-07-01
影响因子：
4.4
通讯作者：
Suzuki, Haruhiko
中科院分区：
文献类型：
--
作者：
Rifa'i, Muhaimin;Shi, Zhe;Suzuki, Haruhiko
CD 8（+）CD 122（+）调节性T细胞（CD 8（+）CD 122（+）Treg）是天然存在的Treg，其有效抑制CD 8（+）和CD 4（+）靶细胞的增殖和IFN-γ产生。本研究使用重建这些细胞的调节作用的体外培养系统，研究了CD 8（+）CD 122（+）Treg识别靶细胞的分子机制。与预活化的T细胞共培养的初始CD 8（+）CD 122（+）Treg成为产生IL-10并抑制来自靶T细胞的IFN-γ产生的活性Treg。CD 8（+）CD 122（+）Treg有效抑制同基因小鼠品系靶细胞的IFN-γ产生，但不抑制具有不相容MHC的同种异体小鼠品系的IFN-γ产生。通过使用MHC同源小鼠品系，进一步证实了CD 8（+）CD 122（+）Treg的MHC限制性抑制。通过特异性阻断抗体对Treg或靶细胞上的细胞表面分子的阻断表明H-2K、H-2D、α β TCR和CD 8参与调节作用，但I-A和Qa-1不参与。这些结果表明，CD 8（+）CD 122（+）Treg通过与常规MHC I类-α β TCR的相互作用识别已经活化的T细胞，并成为产生IL-10并抑制靶细胞的活性调节细胞。
CD8(+)CD122(+) regulatory T cells (CD8(+)CD122(+) Treg) are naturally occurring Treg that effectively suppress the proliferation and IFN-gamma production of both CD8(+) and CD4(+) target cells. This study investigated the molecular mechanisms of the recognition of target cells by CD8(+)CD122(+) Treg using an in vitro culture system that reconstitutes the regulatory action of these cells. Naive CD8(+)CD122(+) Treg co-cultured with pre-activated T cells became active Treg that produced IL-10 and suppressed IFN-gamma production from the target T cells. CD8(+)CD122(+) Treg effectively suppressed the IFN-gamma production of the target cells of syngeneic mouse strains but not of allogeneic mouse strains with incompatible MHC. By using MHC-congeneic mouse strains, MHC-restricted suppression by CD8(+)CD122(+) Treg was further confirmed. The blockade of cell surface molecules either on the Treg or on the target cells by specific blocking antibodies indicated that H-2K, H-2D, alpha beta TCR and CD8 were involved in the regulatory action but I-A and Qa-1 were not. These results indicate that CD8(+)CD122(+) Treg recognize already-activated T cells via the interaction of conventional MHC class I-alpha beta TCR and become active regulatory cells that produce IL-10 and suppress the target cells.