Positive selection of extrathymically developed T cells by self-antigens.
Positive selection of extrathymically developed T cells by self-antigens.
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DOI：
10.1084/jem.188.4.779
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发表时间：
1998-08-17
影响因子：
15.3
通讯作者：
Nomoto, K
中科院分区：
文献类型：
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作者：
Yamada, H;Ninomiya, T;Hashimoto, A;Tamada, K;Takimoto, H;Nomoto, K
大多数T细胞通过胸腺发育，在那里它们经历阳性和阴性选择。已知一些外周T细胞在没有胸腺的情况下发育，但关于其选择的信息不足。为了分析胸腺外发育的T细胞的选择，我们用雄性H-Y抗原特异性T细胞受体（TCR）转基因小鼠的骨髓细胞重建胸腺切除的雄性或雌性受体小鼠。结果表明，携带自身抗原特异性TCR的T细胞在胸腺切除的男性受者中没有缺失。更重要的是，H-Y抗原特异性T细胞的胸腺切除女性受体的情况下，表明胸腺外发育的T细胞的自身抗原的阳性选择。雄性小鼠胸腺外发育的T细胞表达白细胞介素（IL）-2受体β链（IL-2 R β）和中等水平的CD 3（CD 3 int），但为自然杀伤细胞（NK）1.1−。在TCR交联后，它们迅速产生干扰素γ，但不产生IL-4。此外，在正常小鼠的CD 3 intIL-2 R β+NK1.1−细胞中观察到类似的细胞因子产生模式，这些细胞已被证明是胸腺外发育的。这些结果表明，正常小鼠胸腺外发育的CD 3 intIL-2 R β+NK1.1−细胞也被自身抗原阳性选择。
Most T cells develop through the thymus, where they undergo positive and negative selection. Some peripheral T cells are known to develop in the absence of thymus, but there is insufficient information about their selection. To analyze the selection of extrathymically developed T cells, we reconstituted thymectomized male or female recipient mice with bone marrow cells of mice transgenic for male H-Y antigen–specific T cell receptor (TCR). It was revealed that the T cells bearing self-antigen–specific TCR were not deleted in thymectomized male recipients. More importantly, the absence of H-Y antigen–specific T cells in thymectomized female recipients suggests positive selection of extrathymically developed T cells by the self-antigen. The extrathymically developed T cells in male mice expressed interleukin (IL)-2 receptor β chain (IL-2Rβ) and intermediate levels of CD3 (CD3int) but were natural killer cell (NK)1.1−. They rapidly produced interferon γ but not IL-4 after TCR cross-linking. Furthermore, a similar pattern of cytokine production was observed in CD3intIL-2Rβ+NK1.1− cells in normal mice which have been shown to develop extrathymically. These results suggest that extrathymically developed CD3intIL-2Rβ+NK1.1− cells in normal mice are also positively selected by self-antigens.