The SLAM-Associated protein signaling pathway is required for development of CD4+ T cells selected by homotypic thymocyte interaction
The SLAM-Associated protein signaling pathway is required for development of CD4+ T cells selected by homotypic thymocyte interaction
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DOI：
10.1016/j.immuni.2007.10.008
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发表时间：
2007-11-01
期刊：
影响因子：
32.4
通讯作者：
Chang, Cheong-Hee
中科院分区：
文献类型：
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作者：
Li, Wei;Sofi, M. Hanief;Chang, Cheong-Hee
表达MHC II类双阳性胸腺细胞与皮质胸腺上皮细胞一样有效地诱导CD 4（+）T细胞发育的进展。由于表达CD 1d的双阳性胸腺细胞选择自然杀伤T（NKT）细胞，我们研究了胸腺细胞选择的CD 4（+）（T-CD 4）T细胞是否需要与NKT细胞相同的信号成分。使用骨髓嵌合体，我们发现信号分子SAP，Fyn和PKC θ是T-CD 4 T细胞生成所必需的，而Ly 108受体，白细胞介素-15受体α或转录因子T-bet的突变具有边际效应。此外，SAP对于T-CD 4 T细胞产生IL-4是至关重要的，但PKC θ缺陷并不改变T-CD 4 T细胞产生细胞因子的能力。无论选择途径如何，T-bet都是产生最大量的IFN-γ给CD 4（+）T细胞所必需的。因此，与上皮细胞选择的CD 4（+）T细胞相反，胸腺细胞选择的两种不同的T细胞谱系，即，T-CD 4和NKT细胞都利用SAP-Fyn-PKC θ途径进行发育和功能。
MHC class II-expressing double-positive thymocytes induce progression of CD4(+) T cell development as efficiently as cortical thymic epithelial cells do. Because double-positive thymocytes expressing CD1d select natural killer T (NKT) cells, we investigated whether thymocyte-selected CD4(+) (T-CD4) T cells require the same signaling components as NKT cells. Using bone-marrow chimeras, we found that the signaling molecules SAP, Fyn, and PKC theta were essential for T-CD4 T cell generation, whereas mutations in the Ly108 receptor, interleukin-15 receptor alpha, or the transcription factor T-bet had a marginal effect. Furthermore, SAP was critical for IL-4 production by T-CD4 T cells, but the PKC theta deficiency did not alter the ability of T-CD4 T cells to produce cytokines. T-bet was necessary to produce the maximum amount of IFN-gamma for CD4(+) T cells regardless of the selection pathway. Thus, in contrast to epithelial cell-selected CD4(+) T cells, the two distinct lineages of T cells selected by thymocytes-i.e., T-CD4 and NKT cells-both utilize the SAP-Fyn-PKC theta pathway for their development and function.