The CD28H/B7-H5 pathway is a newly identified pathway of the B7 family. In human peripheral blood, the receptor CD28H is preferentially expressed on naïve T cells and repetitive stimulation of T cells leads to the loss of CD28H expression. Here we examined the expression of the CD28H/B7-H5 pathway in human peripheral tissues, as well as in human cancers. We found that CD28H is preferentially expressed on T cells with tissue-resident phenotypes (TRM). Supporting that, stimulation via IL-15 and TGF-β, presumably major cytokines essential for TRM cell homeostasis, sustains CD28H expression on T cells. The ligand B7-H5 is constitutively expressed on normal epithelium of human oral-gastrointestinal tracts. In human cancers, CD28H is preferentially present on tumor infiltrating lymphocytes (TILs) with TRM features and identifies a TRM subset with less cytotoxicity. Taken together, our studies suggest that the CD28H/B7-H5 pathway involves the interactions between TRM cells and epithelium, and could be important for human TRM homeostasis and function.

中文翻译：

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CD28H的表达鉴定出在人类外周组织和癌症中具有较小细胞毒性的常驻记忆CD8 + T细胞。

CD28H / B7-H5途径是B7家族的新发现途径。在人类外周血中，受体CD28H在幼稚T细胞上优先表达，并且反复刺激T细胞导致CD28H表达丧失。在这里，我们检查了CD28H / B7-H5途径在人类外周组织以及人类癌症中的表达。我们发现CD28H优先在具有组织驻留表型（TRM）的T细胞上表达。支持这一点的是，通过IL-15和TGF-β（可能是TRM细胞稳态所需的主要细胞因子）进行的刺激，可以维持CD28H在T细胞上的表达。配体B7-H5在人口腔-胃肠道的正常上皮中组成性表达。在人类癌症中 CD28H优先存在于具有TRM特征的肿瘤浸润淋巴细胞（TIL）上，并鉴定出具有较小细胞毒性的TRM亚型。两者合计，我们的研究表明CD28H / B7-H5通路涉及TRM细胞与上皮细胞之间的相互作用，可能对人类TRM的稳态和功能很重要。