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

C Passaes, A Millet, V Madelain, V Monceaux, A David… - Cell Reports, 2020 - cell.com
C Passaes, A Millet, V Madelain, V Monceaux, A David, P Versmisse, N Sylla, E Gostick…
Cell Reports, 2020cell.com
Highly efficient CD8+ T cells are associated with natural HIV control, but it has remained
unclear how these cells are generated and maintained. We have used a macaque model of
spontaneous SIVmac251 control to monitor the development of efficient CD8+ T cell
responses. Our results show that SIV-specific CD8+ T cells emerge during primary infection
in all animals. The ability of CD8+ T cells to suppress SIV is suboptimal in the acute phase
but increases progressively in controller macaques before the establishment of sustained …
Summary
Highly efficient CD8+ T cells are associated with natural HIV control, but it has remained unclear how these cells are generated and maintained. We have used a macaque model of spontaneous SIVmac251 control to monitor the development of efficient CD8+ T cell responses. Our results show that SIV-specific CD8+ T cells emerge during primary infection in all animals. The ability of CD8+ T cells to suppress SIV is suboptimal in the acute phase but increases progressively in controller macaques before the establishment of sustained low-level viremia. Controller macaques develop optimal memory-like SIV-specific CD8+ T cells early after infection. In contrast, a persistently skewed differentiation phenotype characterizes memory SIV-specific CD8+ T cells in non-controller macaques. Accordingly, the phenotype of SIV-specific CD8+ T cells defined early after infection appears to favor the development of protective immunity in controllers, whereas SIV-specific CD8+ T cells in non-controllers fail to gain antiviral potency, feasibly as a consequence of early defects imprinted in the memory pool.
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