Thymocyte-thymocyte interaction for efficient positive selection and maturation of CD4 T cells

Thymocyte-thymocyte interaction for efficient positive selection and maturation of CD4 T cells
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DOI:
10.1016/j.immuni.2005.09.005
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发表时间:
2005-10-01
期刊:
影响因子:
32.4
通讯作者:
Park, SH
Park, SH
中科院分区:
医学1区
文献类型:
--
作者:
Choi, EY;Jung, KC;Park, SH

文献摘要

被引文献

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尽管有许多关于来自包括人类在内的广泛哺乳动物物种的T细胞表达MHC II类的报道,但这种现象的生物学相关性从未用适当设计的动物模型进行过测试。为了解决这个问题,我们开发了小鼠模型,其中未成熟胸腺细胞是胸腺中唯一的正选择抗原呈递细胞。在这些小鼠中,产生了具有适当成熟表型的CD 4(+)T细胞,并显示出TCR V β的多样性。CD 4(+)T细胞具有功能活性,介导涉及多克隆TCR V β的有效同种异体应答。这些结果表明,胸腺细胞-胸腺细胞(T-T)的相互作用作为一个独立的途径选择CD 4(+)T细胞在胸腺的物种与MHC II阳性胸腺细胞。这种T-T相互作用似乎是在异种宿主中产生供体MHC限制性CD 4(+)T细胞的基础。
Despite numerous reports on MHC class II expression by T cells from a wide spectrum of mammalian species including humans, the biological relevance of this phenomenon has never been tested with appropriately designed animal models. To address this issue, we developed mouse models in which immature thymocytes are the only positively selecting antigen-presenting cells in the thymus. In these mice, CD4(+) T cells were generated with the appropriate maturation phenotype and showed a diverse repertoire of TCR V beta s. The CD4(+) T cells were functionally competent, mediating effective allogeneic responses that involved polyclonal TCR V beta s. These results suggest that the thymocyte-thymocyte (T-T) interaction operates as an independent pathway for CD4(+) T cell selection in the thymi of species with MHC II-positive thymocytes. This T-T interaction appears to be the basis for the generation of donor MHC-restricted CD4(+) T cells in xenogeneic hosts.