CD49d marks Th1 and Tfh-like antigen-specific CD4+ T cells during Plasmodium chabaudi infection
CD49d marks Th1 and Tfh-like antigen-specific CD4+ T cells during Plasmodium chabaudi infection
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DOI：
10.1093/intimm/dxab020
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发表时间：
2021-04-29
影响因子：
4.4
通讯作者：
Yui, Katsuyuki
中科院分区：
文献类型：
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作者：
Jian, Jiun-Yu;Inoue, Shin-Ichi;Yui, Katsuyuki
活化后，特异性CD 4（+）T细胞上调病原体特异性CD 4（+）T细胞的替代标志物CD 11 a和CD 49 d的表达。然而，使用对疟原虫抗原特异性的T细胞受体转基因小鼠，称为PbT-II，我们发现在急性疟原虫感染期间，活化的CD 4（+）T细胞不仅发育为CD 11 a（hi）CD 49 d（hi）细胞，而且发育为CD 11 a（hi）CD 49 d（lo）细胞。CD 49 d（hi）PbT-II细胞定位于脾红髓，表达转录因子T-bet并产生IFN-γ，表明它们是1型辅助性T（Th 1）细胞。相反，CD 49 d（lo）PbT-II细胞位于白色髓/边缘区，是一个异质性群体，其中约一半表达CXCR 5，三分之一表达Bcl-6，这是滤泡辅助T（Tfh）细胞的主要调节因子。在过继转移实验中，CD 49 d（hi）和CD 49 d（lo）PbT-II细胞在用抗原脉冲的树突状细胞刺激后均分化为CD 49 d（hi）Th 1型细胞，而CD 49 d（hi）和CD 49 d（lo）表型通常在感染夏氏疟原虫的小鼠中保持。这些结果表明，CD 49 d表达于Th 1型疟原虫特异性CD 4（+）T细胞，其定位于脾的红髓中，并且可以用作抗原特异性Th 1 CD 4（+）T细胞的标记，而不是所有病原体特异性CD 4（+）T细胞的标记。
Upon activation, specific CD4(+) T cells up-regulate the expression of CD11a and CD49d, surrogate markers of pathogen-specific CD4(+) T cells. However, using T-cell receptor transgenic mice specific for a Plasmodium antigen, termed PbT-II, we found that activated CD4(+) T cells develop not only to CD11a(hi)CD49d(hi) cells, but also to CD11a(hi)CD49d(lo) cells during acute Plasmodium infection. CD49d(hi) PbT-II cells, localized in the red pulp of spleens, expressed transcription factor T-bet and produced IFN-gamma, indicating that they were type 1 helper T (Th1)-type cells. In contrast, CD49d(lo) PbT-II cells resided in the white pulp/marginal zones and were a heterogeneous population, with approximately half of them expressing CXCR5 and a third expressing Bcl-6, a master regulator of follicular helper T (Tfh) cells. In adoptive transfer experiments, both CD49d(hi) and CD49d(lo) PbT-II cells differentiated into CD49d(hi) Th1-type cells after stimulation with antigen-pulsed dendritic cells, while CD49d(hi) and CD49d(lo) phenotypes were generally maintained in mice infected with Plasmodium chabaudi. These results suggest that CD49d is expressed on Th1-type Plasmodium-specific CD4(+) T cells, which are localized in the red pulp of the spleen, and can be used as a marker of antigen-specific Th1 CD4(+) T cells, rather than that of all pathogen-specific CD4(+) T cells.