Expression of the monocarboxylate transporter MCT1 is required for virus-specific CD8+ T cell memory development
(2024) Proceedings of the National academy of sciences of the United States of America — Vol. 121, n° 13, p. e2306763121 (2024)
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- 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, 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 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.
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D’aria, S., Maquet, C., Li, S., Dhup, S., Lepez, A., Kohler, A., Van Hee, V., Dadhich, R., Freniere, M., Andris, F., Nemazanyy, I., Sonveaux, P., Machiels, B., Gillet, L., & Braun, M. (2024). Expression of the monocarboxylate transporter MCT1 is required for virus-specific CD8+ T cell memory development. Proceedings of the National academy of sciences of the United States of America, 121(13), e2306763121. https://hdl.handle.net/2078.5/241485 (Original work published 2024)