Cell Reports
Volume 32, Issue 12, 22 September 2020, 108174
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Article
Optimal Maturation of the SIV-Specific CD8+ T Cell Response after Primary Infection Is Associated with Natural Control of SIV: ANRS SIC Study

https://doi.org/10.1016/j.celrep.2020.108174Get rights and content
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Highlights

  • SIV-specific CD8+ T cells in acute infection show poor SIV-suppressive activity ex vivo

  • SIV-suppressive activity increases over time in SIV controllers preceding viral control

  • Controllers develop memory-like CD8+ T cells, which seems to favor protective immunity

  • Cells from non-controllers have a skewed phenotype and fail to gain antiviral potential

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.

Keywords

HIV
SIV
natural control
elite controllers
T cell memory
CD8+ T cells
cytotoxic T cells
pathogenesis
antiviral function
HIV/SIV suppression

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These authors contributed equally

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