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

Autor:	D'Aria S; Institute for Medical Immunology, Faculty of Medicine, Université libre de Bruxelles, Gosselies 6041, Belgium., Maquet C; Immunology-Vaccinology, Department of Infectious and Parasitic Diseases, Faculty of Veterinary Medicine - Fundamental and Applied Research for Animals & Health Research Unit, University of Liège, Liège 4000, Belgium., Li S; Institute for Medical Immunology, Faculty of Medicine, Université libre de Bruxelles, Gosselies 6041, Belgium., Dhup S; Pole of Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels 1200, Belgium., Lepez A; Immunobiology Laboratory, Faculty of Sciences, Université libre de Bruxelles, Gosselies 6041, Belgium., Kohler A; Institute for Medical Immunology, Faculty of Medicine, Université libre de Bruxelles, Gosselies 6041, Belgium., Van Hée VF; Pole of Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels 1200, Belgium., Dadhich RK; Pole of Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels 1200, Belgium., Frenière M; Institute for Medical Immunology, Faculty of Medicine, Université libre de Bruxelles, Gosselies 6041, Belgium., Andris F; Immunobiology Laboratory, Faculty of Sciences, Université libre de Bruxelles, Gosselies 6041, Belgium., Nemazanyy I; Plateforme d'étude du métabolisme, Institut Necker, Inserm US 24 - CNRS UMS 3633, Faculté de Médecine Paris Descartes, Paris 75015, France., Sonveaux P; WEL Research Institute, Welbio Department, Wavre 1300, Belgium., Machiels B; Immunology-Vaccinology, Department of Infectious and Parasitic Diseases, Faculty of Veterinary Medicine - Fundamental and Applied Research for Animals & Health Research Unit, University of Liège, Liège 4000, Belgium., Gillet L; Immunology-Vaccinology, Department of Infectious and Parasitic Diseases, Faculty of Veterinary Medicine - Fundamental and Applied Research for Animals & Health Research Unit, University of Liège, Liège 4000, Belgium., Braun MY; Institute for Medical Immunology, Faculty of Medicine, Université libre de Bruxelles, Gosselies 6041, Belgium.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Mar 26; Vol. 121 (13), pp. e2306763121. Date of Electronic Publication: 2024 Mar 18.
DOI:	10.1073/pnas.2306763121
Abstrakt:	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 γ-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 γ-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. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
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