CD98 Heavy Chain Is a Potent Positive Regulator of CD4+ T Cell Proliferation and Interferon-γ Production In Vivo.
CD98 Heavy Chain Is a Potent Positive Regulator of CD4+ T Cell Proliferation and Interferon-γ Production In Vivo.
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DOI：
10.1371/journal.pone.0139692
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Yasutomo K
中科院分区：
文献类型：
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作者：
Kurihara T;Arimochi H;Bhuyan ZA;Ishifune C;Tsumura H;Ito M;Ito Y;Kitamura A;Maekawa Y;Yasutomo K
在它们识别由MHC呈递的抗原后，T细胞增殖对于克隆扩增和获得效应子功能是至关重要的，这对于建立适应性免疫应答是必需的。CD 98重链（CD 98 hc，Slc 3a 2）在CD 4+和CD 8 + T细胞的增殖中起着至关重要的作用，尽管目前尚不清楚CD 98 hc是否直接调节与体内T细胞增殖无关的T细胞效应功能。在这里，我们证明，CD 98 hc是所需的CD 4 + T细胞增殖和Th 1功能分化。T细胞特异性CD 98 hc缺失不影响胸腺中T细胞的发育。与对照T细胞相比，CD 98 hc缺陷型CD 4 + T细胞在体内增殖更慢。CD 4 + T细胞中缺乏CD 98 hc的C57 BL/6小鼠即使在大量CD 4 + T细胞增殖的情况下，由于IFN-γ产生降低，也不能控制主要利什曼原虫感染。与野生型T细胞相比，CD 98 hc缺陷型CD 4 + T细胞表现出较低的IFN-γ产生，即使在比较经历相同细胞分裂次数的细胞中的IFN-γ表达时也是如此。因此，这些数据表明，CD 98 hc是所需的CD 4 + T细胞的扩增和功能性Th 1分化在体内，并建议，CD 98 hc可能是一个很好的目标，用于治疗Th 1介导的免疫疾病。
Upon their recognition of antigens presented by the MHC, T cell proliferation is vital for clonal expansion and the acquisition of effector functions, which are essential for mounting adaptive immune responses. The CD98 heavy chain (CD98hc, Slc3a2) plays a crucial role in the proliferation of both CD4+ and CD8+ T cells, although it is unclear if CD98hc directly regulates the T cell effector functions that are not linked with T cell proliferation in vivo. Here, we demonstrate that CD98hc is required for both CD4+ T cell proliferation and Th1 functional differentiation. T cell-specific deletion of CD98hc did not affect T cell development in the thymus. CD98hc-deficient CD4+ T cells proliferated in vivo more slowly as compared with control T cells. C57BL/6 mice lacking CD98hc in their CD4+ T cells could not control Leishmania major infections due to lowered IFN-γ production, even with massive CD4+ T cell proliferation. CD98hc-deficient CD4+ T cells exhibited lower IFN-γ production compared with wild-type T cells, even when comparing IFN-γ expression in cells that underwent the same number of cell divisions. Therefore, these data indicate that CD98hc is required for CD4+ T cell expansion and functional Th1 differentiation in vivo, and suggest that CD98hc might be a good target for treating Th1-mediated immune disorders.