Kared Hassen, Tan Crystal, Narang Vipin, Tan Shu Wen, Xian Chin Hui, Wei Alicia Tay Seok, Lum Josephine, Ruiz-Mateos Ezequiel, Rajasuriar Reena, Kamarulzaman Adeeba, Ng Tze Pin, Larbi Anis
Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), Immunos Building, 8A Biomedical Grove, Biopolis, Republic of Singapore.
Department of Immunology, Oslo University Hospital, Oslo, Norway.
Sci Rep. 2024 Dec 28;14(1):30779. doi: 10.1038/s41598-024-80971-5.
Long-term control of viral replication relies on the efficient differentiation of memory T cells into effector T cells during secondary immune responses. Recent findings have identified T cell precursors for both memory and exhausted T cells, suggesting the existence of progenitor-like effector T cells. These cells can persist without antigenic challenge but expand and acquire effector functions upon recall immune responses. In this study, we demonstrate that the combination of SLAMF7 with either CD27 or TCF-1 effectively identifies progenitor-like effector CD8 T cells, while SLAMF7 with GPR56 or TOX defines effector CD8 T cells. These markers allow for the clear segregation of these distinct cell subsets. SLAMF7 CD8T cells are dynamically modulated during viral infections, including HIV, HCV, CMV, and SARS-CoV-2, as well as during aging. We further characterize the SLAMF7 signature at both phenotypic and transcriptional levels. Notably, during aging, the SLAMF7 pathway becomes dysregulated, resulting in persistent phosphorylation of STAT1. Additionally, SLAMF7 ligation in the presence of IL-15 induces TCF-1 expression, which promotes the homeostatic proliferation of progenitor-like effector CD8 T cells.
病毒复制的长期控制依赖于在二次免疫反应期间记忆T细胞有效地分化为效应T细胞。最近的研究发现已经确定了记忆T细胞和耗竭T细胞的T细胞前体，这表明存在祖细胞样效应T细胞。这些细胞可以在没有抗原刺激的情况下持续存在，但在再次免疫反应时会扩增并获得效应功能。在本研究中，我们证明SLAMF7与CD27或TCF-1的组合能够有效地识别祖细胞样效应CD8 T细胞，而SLAMF7与GPR56或TOX则可定义效应CD8 T细胞。这些标志物能够清晰地分离这些不同的细胞亚群。在包括HIV、HCV、CMV和SARS-CoV-2在内的病毒感染期间以及衰老过程中，SLAMF7+ CD8 T细胞会受到动态调节。我们进一步在表型和转录水平上对SLAMF7特征进行了表征。值得注意的是，在衰老过程中，SLAMF7通路失调，导致STAT1持续磷酸化。此外，在IL-15存在的情况下，SLAMF7的连接会诱导TCF-1表达，从而促进祖细胞样效应CD8 T细胞的稳态增殖。
