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Optimal maturation of the SIV-specific CD8+ T-cell response after primary infection is associated with natural control of SIV. ANRS SIC study

By Caroline Passaes, Antoine Millet, Vincent Madelain, Valérie Monceaux, Annie David, Pierre Versmisse, Naya Sylla, Emma Gostick, David A. Price, Antoine Blancher, Nathalie Dereuddre-Bosquet, Gianfranco Pancino, Roger Le Grand, Olivier Lambotte, Michaela Müller-Trutwin, Christine Rouzioux, Jeremie Guedj, Veronique Avettand-Fenoel, Bruno Vaslin, Asier Sáez-Cirión

Posted 21 Dec 2019
bioRxiv DOI: 10.1101/2019.12.20.885459 (published DOI: 10.1016/j.celrep.2020.108174)

Highly efficient virus-specific CD8+ T-cells are associated with immune control of HIV infection, but it remains unclear how these cells are generated and maintained over time. We used a macaque model of spontaneous control of SIVmac251 infection to monitor the development and evolution of potent antiviral CD8+ T-cell responses. SIV-specific CD8+ T-cells emerged during primary infection in all animals. However, the ability of CD8+ T cells to suppress SIV replication was low in early stages but increased after a period of maturation, temporally linked with the establishment of sustained low-level viremia in controller macaques. SIV-specific CD8+ T-cells with a central memory phenotype expressed higher levels of survival markers in controllers versus non-controllers. In contrast, a persistently skewed differentiation phenotype was observed among central memory SIV-specific CD8+ T-cells in non-controllers since primary infection, typified by relatively high expression levels of T-bet. Collectively, these data show that the phenotype of SIV-specific CD8+ T-cells defined early after SIV infection favor the gain of antiviral potency as a function of time in controllers, whereas SIV-specific CD8+ T-cell responses in non-controllers fail to gain antiviral potency due to early defects imprinted in the central memory pool.

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