Choi Eun Young, Jung Kyeong Cheon, Park Hyo Jin, Chung Doo Hyun, Song Jin Sook, Yang Seung Don, Simpson Elizabeth, Park Seong Hoe
Graduate Program of Immunology, Seoul National University College of Medicine, Seoul 110-799, Korea.
Immunity. 2005 Oct;23(4):387-96. doi: 10.1016/j.immuni.2005.09.005.
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 Vbetas. The CD4+ T cells were functionally competent, mediating effective allogeneic responses that involved polyclonal TCR Vbetas. 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.
尽管有大量关于包括人类在内的多种哺乳动物T细胞表达MHC II类分子的报道，但这一现象的生物学相关性从未通过适当设计的动物模型进行过测试。为了解决这个问题，我们构建了小鼠模型，其中未成熟胸腺细胞是胸腺中唯一进行阳性选择的抗原呈递细胞。在这些小鼠中，产生了具有适当成熟表型的CD4+ T细胞，并表现出多样化的TCR Vβ库。CD4+ T细胞功能正常，介导涉及多克隆TCR Vβ的有效的同种异体反应。这些结果表明，胸腺细胞-胸腺细胞（T-T）相互作用作为MHC II阳性胸腺细胞物种胸腺中CD4+ T细胞选择的独立途径发挥作用。这种T-T相互作用似乎是异种宿主中产生供体MHC限制性CD4+ T细胞的基础。
