德国慕尼黑工业大学Dietmar Zehn等研究人员合作发现，耗竭T细胞的前体在急性感染中被预先形成。2025年1月8日，《自然》杂志在线发表了这项成果。

研究人员表示，T细胞耗竭限制了效应T细胞在慢性感染和肿瘤中的功能。通常认为，这些功能低下的T细胞及其前体的形成需要刺激性条件，而这些条件仅在持续暴露于抗原和炎症时才会出现。

与此形成鲜明对比的是，研究人员在急性感染的早期阶段发现了类似的T细胞群体。在这一阶段，早期发育的TCF1⁺前体群体表现出出乎意料的多样性，其中包括正常记忆T细胞的前体，但也包括具有类似于慢性感染中发现的耗竭T细胞前体的表型、基因表达和表观遗传特征的细胞。研究人员证明，高亲和力配体促进了这些前体的形成，而PD-1信号通路则限制了其发育。尽管这些耗竭前体在感染初期常常被发现，但在免疫系统能够解决的感染中，它们会减少并最终不会完全丧失。

因此，研究人员得出结论，无论感染的结果如何，具有至少两种不同表型的前体T细胞是预先生成的。

附：英文原文

Title: Precursors of exhausted T cells are preemptively formed in acute infection

Author: Chu, Talyn, Wu, Ming, Hoellbacher, Barbara, de Almeida, Gustavo P., Wurmser, Christine, Berner, Jacqueline, Donhauser, Lara V., Ann-Katrin, Gerullis, Lin, Siran, Cepeda-Mayorga, J. Diego, Kilb, Iman I., Bongers, Lukas, Toppeta, Fabio, Strobl, Philipp, Youngblood, Ben, Schulz, Anna M., Zippelius, Alfred, Knolle, Percy A., Heinig, Matthias, Hackstein, Carl-Philipp, Zehn, Dietmar

Issue&Volume: 2025-01-08

Abstract: T cell exhaustion limits effector T cell function in chronic infection and tumors1,2. The development of these hypofunctional T cells and of their precursors was considered to require stimulatory conditions met only upon persisting exposure to antigen and inflammation. In sharp contrast, we found similar T cell populations in the early phase of acute infections1,2. At that stage early developing TCF1+ precursor population shows an unexpected diversity, which includes precursors of normal memory T cells but also cells with a phenotype, gene-expression, and epigenetic profile that resembles precursors of exhausted T cells found in chronic infections. We demonstrate that high ligand affinity promotes, and PD-1 signaling restricts the development of these precursors. While these exhausted precursors are initially frequently found, they decline without being completely lost in infections the immune system resolves. We therefore concluded that precursor T cells with at least two distinct phenotypes are preemptively generated irrespectively of the outcome of the infection.

DOI: 10.1038/s41586-024-08451-4

Source: https://www.nature.com/articles/s41586-024-08451-4