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Pré-Publication, Document De Travail Année : 2020

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

Emma Gostick
  • Fonction : Auteur
David Price
  • Fonction : Auteur

Résumé

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.

Domaines

Immunologie
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pasteur-02865346 , version 1 (11-06-2020)

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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⟩

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