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

Caroline Passaes (1, 2) , Antoine Millet (3) , Vincent Madelain (4) , Valerie Monceaux (1) , Annie David (1) , Pierre Versmisse (1) , Naya Sylla (2) , Emma Gostick (5) , David Price (5) , Antoine Blancher (6, 7) , Nathalie Dereuddre-Bosquet (2) , Gianfranco Pancino (1) , Roger Le Grand (2) , Olivier Lambotte (8, 2, 9) , Michaela Müller-Trutwin (1) , Christine Rouzioux (10, 11, 3) , Jérémie Guedj (4) , Veronique Avettand-Fenoel (11, 3) , Bruno Vaslin (2) , Asier Sáez-Cirión (1)

1 HIV, Inflammation et persistance - HIV, Inflammation and Persistence
2 IDMIT - Infectious Diseases Models for Innovative Therapies
3 UPCité UFR Médecine - Université Paris Cité - UFR Médecine [Santé]
4 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
5 Cardiff University
6 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
7 CPTP - Centre de Physiopathologie Toulouse Purpan
8 Service de médecine interne et maladies infectieuses
9 Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre]
10 Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant
11 Service de Microbiologie Clinique [Paris]

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.

Domains: Life Sciences [q-bio]; Immunology

Caroline Passaes, Antoine Millet, Vincent Madelain, Valerie Monceaux, Annie David, et al.. Optimal maturation of the SIV-specific CD8 + T-cell response after primary infection is associated with natural control of SIV. ANRS SIC study.. 2020. ⟨pasteur-02865346⟩