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IL2Rβ-dependent signals drive terminal exhaustion and suppress memory development during chronic viral infection

Beltra, Jean-Christophe; Bourbonnais, Sara; Bedard, Nathalie; Charpentier, Tania; Boulangé, Moana; Michaud, Eva; Boufaied, Ines; Bruneau, Julie; Shoukry, Naglaa H; Lamarre, Alain; Decaluwe, Hélène (2016). IL2Rβ-dependent signals drive terminal exhaustion and suppress memory development during chronic viral infection Proceedings of the National Academy of Sciences of the United States of America . DOI: 10.1073/pnas.1604256113.

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Résumé

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Exhaustion of CD8+ T cells severely impedes the adaptive immune response to chronic viral infections. Despite major advances in our understanding of the molecular regulation of exhaustion, the cytokines that directly control this process during chronicity remain unknown. We demonstrate a direct impact of IL-2 and IL-15, two common gamma-chain-dependent cytokines, on CD8+ T-cell exhaustion. Common to both cytokine receptors, the IL-2 receptor beta (IL2Rbeta) chain is selectively maintained on CD8+ T cells during chronic lymphocytic choriomeningitis virus and hepatitis C virus infections. Its expression correlates with exhaustion severity and identifies terminally exhausted CD8+ T cells both in mice and humans. Genetic ablation of the IL2Rbeta chain on CD8+ T cells restrains inhibitory receptor induction, in particular 2B4 and Tim-3; precludes terminal differentiation of highly defective PD-1hi effectors; and rescues memory T-cell development and responsiveness to IL-7-dependent signals. Together, we ascribe a previously unexpected role to IL-2 and IL-15 as instigators of CD8+ T-cell exhaustion during chronic viral infection.

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Informations complémentaires: Résumé avec symboles
Mots-clés libres: CD8; T cell; IL-2; IL-15; exhaustion; memory T cell
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 12 oct. 2016 20:10
Dernière modification: 21 déc. 2016 14:10
URI: http://espace.inrs.ca/id/eprint/4625

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