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

Jean-Christophe Beltra 1, 2 Sara Bourbonnais 2 Nathalie Bédard 3 Tania Charpentier 4 Moana Boulangé 2 Eva Michaud 2 Ines Boufaied 2 Julie Bruneau 1, 3 Naglaa H Shoukry 1, 3 Alain Lamarre 4 Hélène Decaluwe 2, 1
1 Université de Montréal - UdeM (CANADA)
2 Research Center, CHU Sainte-Justine, Universite de Montreal, Montreal, Quebec, Canada
Centre de recherche de l'hôpital Sainte Justine
3 CRCHUM - University of Montreal Hospital Research Center
4 INRS-IAF - Institut Armand Frappier
Abstract : 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 β (IL2Rβ) 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 IL2Rβ chain on CD8(+) T cells restrains inhibitory receptor induction, in particular 2B4 and Tim-3; precludes terminal differentiation of highly defective PD-1(hi) 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.
Keywords : CD8 T cell IL-15 IL-2 exhaustion memory T cell
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Article dans une revue
Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2016, 113 (37), pp.E5444-53. 〈10.1073/pnas.1604256113〉
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Contributeur : Michel Courcelles <>
Soumis le : mardi 20 décembre 2016 - 16:02:03
Dernière modification le : lundi 5 février 2018 - 15:22:10

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Jean-Christophe Beltra, Sara Bourbonnais, Nathalie Bédard, Tania Charpentier, Moana Boulangé, et al.. 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 , National Academy of Sciences, 2016, 113 (37), pp.E5444-53. 〈10.1073/pnas.1604256113〉. 〈pasteur-01420453〉

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