Antigen-specific T cell repertoire modification of CD4+CD25+ regulatory T cells
Antigen-specific T cell repertoire modification of CD4+CD25+ regulatory T cells
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DOI：
10.4049/jimmunol.172.9.5240
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发表时间：
2004-05-01
影响因子：
4.4
通讯作者：
Yasutomo, K
中科院分区：
文献类型：
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作者：
Hayashi, Y;Tsukumo, SI;Yasutomo, K
T细胞免疫应答由效应T细胞和抑制T细胞之间的相互作用调节。用Ag免疫导致具有针对Ag和MHC的高亲和力TCR的效应CD 4（+）T细胞的选择性扩增和存活。然而，目前尚不清楚，如果CD 4（+）CD 25（+）调节性T细胞（T-reg）识别相同的Ag效应T细胞或Ag特异性TCR库的修改是否发生在T-reg。在这项研究中，我们证明，在一个主要的Ag挑战后，T-reg增殖和TCR库的修改观察，虽然这些反应都低于传统的T细胞。初次抗原激发后抗原特异性T-reg的库修饰增强了T-reg对TCR库修饰的总体抑制功能，但对记忆性CD 4（+）T细胞的增殖没有抑制作用。这些结果表明，针对非自身Ag的T细胞库修饰发生在T-reg中，这对于限制过量的初级和记忆性CD 4（+）T细胞应答至关重要。此外，这些研究提供的证据表明，Ag特异性T-reg的操作是T-reg临床使用的理想策略。
T cell immune responses are regulated by the interplay between effector and suppressor T cells. Immunization with Ag leads to the selective expansion and survival of effector CD4(+) T cells with high affinity TCR against the Ag and MHC. However, it is not known if CD4(+)CD25(+) regulatory T cells (T-reg) recognize the same Ag as effector T cells or whether Ag-specific TCR repertoire modification occurs in T-reg. In this study, we demonstrate that after a primary Ag challenge, T-reg proliferate and TCR repertoire modification is observed although both of these responses were lower than those in conventional T cells. The repertoire modification of Ag-specific T-reg after primary Ag challenge augmented the total suppressive function of T-reg against TCR repertoire modification but not against the proliferation of memory CD4(+) T cells. These results reveal that T cell repertoire modification against a non-self Ag occurs in T-reg, which would be crucial for limiting excess primary and memory CD4(+) T cell responses. In addition, these studies provide evidence that manipulation of Ag-specific T-reg is an ideal strategy for the clinical use of T-reg.