Expression of the monocarboxylate transporter MCT1 is required for virus- specific mouse CD8+T cell memory development

• 成果类型: Article
• 署名作者: D'Aria, Stefania; Maquet, Celine; Li, Shuang; Dhup, Suveera; Lepez, Anouk; Kohler, Arnaud; Hee, Vincent F. Van; Dadhich, Rajesh K.; Freniere, Marine; Andris, Fabienne; Nemazanyy, Ivan; Sonveauxf, Pierre; Machiels, Benedicte; Gillet, Laurent; Braun, Michel Y.
• 署名单位: Universite Libre de Bruxelles; University of Liege; Universite Catholique Louvain; Universite Libre de Bruxelles; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite Paris Cite
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9823
• DOI: 10.1073/pnas.2306763121
• 发表日期: 2024-03-18
• 关键词: cd8(+) t-cells; pneumonia virus; infection; mice; effector; antigen; pd-1; persistence; activation; exhaustion

摘要

Lactate-proton symporter monocarboxylate transporter 1 (MCT1) facilitates lactic acid export from T cells. Here, we report that MCT1 is mandatory for the development of virus- specific CD8+ T cell memory. MCT1- deficient T cells were exposed to acute pneumovirus (pneumonia virus of mice, PVM) or persistent gamma-herpesvirus (Murid herpesvirus 4, MuHV-4) infection. MCT1 was required for the expansion of virus - specific CD8+ T cells and the control of virus replication in the acute phase of infection. This situation prevented the subsequent development of virus- specific T cell memory, a necessary step in containing virus reactivation during gamma-herpesvirus latency. Instead, persistent active infection drove virus- specific CD8+ T cells toward functional exhaustion, a phenotype typically seen in chronic viral infections. Mechanistically, MCT1 deficiency sequentially impaired lactic acid efflux from activated CD8+ T cells, caused an intracellular acidification inhibiting glycolysis, disrupted nucleotide synthesis in the upstream pentose phosphate pathway, and halted cell proliferation which, ultimately, promoted functional CD8+ T cell exhaustion instead of memory development. Taken together, our data demonstrate that MCT1 expression is mandatory for inducing T cell memory and controlling viral infection by CD8+ T cells.