Definition of target antigens for naturally occurring CD4+ CD25+ regulatory T cells
Definition of target antigens for naturally occurring CD4+ CD25+ regulatory T cells
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DOI：
10.1084/jem.20041959
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发表时间：
2005-03-07
影响因子：
15.3
通讯作者：
Shiku, H
中科院分区：
文献类型：
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作者：
Nishikawa, H;Kato, T;Shiku, H
由天然存在的CD 4（+）CD 25（+）调节性T细胞（T reg细胞）识别的抗原靶标一直是难以捉摸的。我们通过重组表达克隆（SEREX）抗原的血清学鉴定，从化学诱导的小鼠肉瘤中定义了一系列广泛表达的自身抗原。用SEREX自身抗原免疫小鼠，其CD 4（+）CD 25（+）T细胞对CD 4（+）CD 25（-）T细胞和CD 8（+）T细胞的肽特异性增殖具有较强的抑制活性。在没有体外T细胞刺激的情况下观察到抑制作用。来自免疫小鼠的这些CD 4（+）CD 25（+）T细胞中的Foxp 3表达比来自幼稚小鼠的CD 4（+）CD 25（+）T细胞高5-10倍。这种抑制作用需要细胞接触，并可被抗糖皮质激素诱导的肿瘤坏死因子受体家族相关基因抗体阻断。在体外抑制活性基本上消失后8周，最后一次免疫。然而，通过用同源自身抗原蛋白体外再刺激而不是用对照蛋白体外再刺激，它被重新获得。我们认为，SEREX定义的自身抗原，如本研究中使用的那些，代表了引发天然存在的CD 4（+）CD 25（+）T reg细胞的自身抗原。
The antigenic targets recognized by naturally occurring CD4(+)CD25(+) regulatory T cells (T reg cells) have been elusive. We have serologically defined a series of broadly expressed self-antigens derived from chemically induced mouse sarcomas by serological identification of antigens by recombinant expression cloning (SEREX). CD4(+)CD25(+)T cells from mice immunized with SEREX-defined self-antigens had strong suppressive activity on peptide-specific proliferation of CD4(+)CD25(-)T cells and CD8(+)T cells. The suppressive effect was observed without in vitro T cell stimulation. Foxp3 expression in these CD4(+)CD25(+)T cells from immunized mice was 5-10 times greater than CD4(+)CD25(+)T cells derived from naive mice. The suppressive effect required cellular contact and was blocked by anti-glucocorticoid-induced tumor necrosis factor receptor family-related gene antibody. In vitro suppressive activity essentially disappeared 8 wk after the last immunization. However, it was regained by in vitro restimulation with cognate self-antigen protein but not with control protein. We propose that SEREX-defined self-antigens such as those used in this study represent self-antigens that elicit naturally occurring CD4(+)CD25(+) T reg cells.