前沿：肝组织驻留记忆 CD4 T 细胞的最佳形成需要 T 细胞特异性转录因子（T-bet）调控 CD18。
Cutting Edge: Optimal Formation of Hepatic Tissue-Resident Memory CD4 T Cells Requires T-bet Regulation of CD18.
机构信息
Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, CA.
出版信息
J Immunol. 2023 Jul 15;211(2):180-185. doi: 10.4049/jimmunol.2300017.
CD4 tissue-resident memory T cells (TRMs) allow robust protection of barrier surfaces against pathogens. We investigated the role of T-bet in the formation of liver CD4 TRMs using mouse models. T-bet-deficient CD4 T cells did not efficiently form liver TRMs when compared with wild-type (WT). In addition, ectopic expression of T-bet enhanced the formation of liver CD4 TRMs, but only when in competition with WT CD4 T cells. Liver TRMs also expressed higher levels of CD18, which was T-bet dependent. The WT competitive advantage was blocked by Ab neutralization of CD18. Taken together, our data show that activated CD4 T cells compete for entry to liver niches via T-bet-induced expression of CD18, allowing TRM precursors to access subsequent hepatic maturation signals. These findings uncover an essential role for T-bet in liver TRM CD4 formation and suggest targeted enhancement of this pathway could increase the efficacy of vaccines that require hepatic TRMs.
CD4 组织驻留记忆 T 细胞（TRMs）可有效保护屏障表面免受病原体侵害。我们使用小鼠模型研究了 T 细胞特异性转录因子（T-bet）在肝脏 CD4 TRMs 形成中的作用。与野生型（WT）相比，T-bet 缺陷型 CD4 T 细胞不能有效地形成肝脏 TRMs。此外，T-bet 的异位表达增强了肝脏 CD4 TRMs 的形成，但仅在与 WT CD4 T 细胞竞争时才如此。肝脏 TRMs 还表达更高水平的 CD18，这依赖于 T-bet。WT 的竞争优势被 CD18 的 Ab 中和阻断。综上所述，我们的数据表明，激活的 CD4 T 细胞通过 T-bet 诱导的 CD18 表达竞争进入肝脏龛位，允许 TRM 前体获得随后的肝成熟信号。这些发现揭示了 T-bet 在肝脏 TRM CD4 形成中的重要作用，并表明靶向增强该途径可能会提高需要肝脏 TRMs 的疫苗的疗效。
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