CD49d 标记疟原虫感染期间的 Th1 和滤泡辅助样抗原特异性 CD4+ T 细胞。

CD49d marks Th1 and Tfh-like antigen-specific CD4+ T cells during Plasmodium chabaudi infection.

机构信息

Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, Japan.

Program for Nurturing Global Leaders in Tropical and Emerging Infectious Diseases, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, Japan.

出版信息

Int Immunol. 2021 Jul 23;33(8):409-422. doi: 10.1093/intimm/dxab020.

DOI:10.1093/intimm/dxab020

PMID:33914894

Abstract

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 CD11ahiCD49dhi cells, but also to CD11ahiCD49dlo cells during acute Plasmodium infection. CD49dhi PbT-II cells, localized in the red pulp of spleens, expressed transcription factor T-bet and produced IFN-γ, indicating that they were type 1 helper T (Th1)-type cells. In contrast, CD49dlo 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 CD49dhi and CD49dlo PbT-II cells differentiated into CD49dhi Th1-type cells after stimulation with antigen-pulsed dendritic cells, while CD49dhi and CD49dlo 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.

摘要

活化后，特定的 CD4+T 细胞上调 CD11a 和 CD49d 的表达，这是病原体特异性 CD4+T 细胞的替代标志物。然而，我们使用针对疟原虫抗原的 T 细胞受体转基因小鼠，称为 PbT-II，发现活化的 CD4+T 细胞在急性疟原虫感染过程中不仅会发育成 CD11ahiCD49dhi 细胞，还会发育成 CD11ahiCD49dlo 细胞。CD49dhi PbT-II 细胞定位于脾脏红髓，表达转录因子 T-bet 并产生 IFN-γ，表明它们是 1 型辅助性 T（Th1）细胞。相比之下，CD49dlo PbT-II 细胞位于白髓/边缘区，是一个异质性群体，其中约一半表达 CXCR5，三分之一表达 Bcl-6，这是滤泡辅助性 T（Tfh）细胞的主要调节因子。在过继转移实验中，CD49dhi 和 CD49dlo PbT-II 细胞在用抗原脉冲树突细胞刺激后均分化为 CD49dhi Th1 型细胞，而在感染疟原虫的小鼠中，CD49dhi 和 CD49dlo 表型通常得以维持。这些结果表明，CD49d 在 Th1 型疟原虫特异性 CD4+T 细胞上表达，这些细胞定位于脾脏的红髓，可作为抗原特异性 Th1 CD4+T 细胞的标志物，而不是所有病原体特异性 CD4+T 细胞的标志物。