Distinct transcriptome profiles of Gag-specific CD8+ T cells temporally correlated with the protection elicited by SIV?nef live attenuated vaccine.

ABSTRACT: The live attenuated vaccine (LAV) SIVmac239?nef (SIV?nef) confers the best protection among all the vaccine modalities tested in rhesus macaque model of HIV-1 infection. This vaccine has a unique feature of time-dependent protection: macaques are not protected at 3-5 weeks post vaccination (WPV), whereas immune protection emerges between 15 and 20 WPV. Although the exact mechanisms of the time-dependent protection remain incompletely understood, studies suggested that both cellular and humoral immunities contribute to this time-dependent protection. To further elucidate the mechanisms of protection induced by SIV?nef, we longitudinally compared the global gene expression profiles of SIV Gag-CM9+ CD8+ (Gag-specific CD8+) T cells from peripheral blood of Mamu-A*01+ rhesus macaques at 3 and 20 WPV using rhesus microarray. We found that gene expression profiles of Gag-specific CD8+ T cells at 20 WPV are qualitatively different from those at 3 WPV. At 20 WPV, the most significant transcriptional changes of Gag-specific CD8+ T cells were genes involved in TCR signaling, differentiation and maturation toward central memory cells, with increased expression of CCR7, TCR?, TCR?, CD28 and decreased expression of CTLA-4, IFN-?, RANTES, granzyme A and B. Our study suggests that a higher quality of SIV-specific CD8+ T cells elicited by SIV?nef over time contributes to the maturation of time-dependent protection.

SUBMITTER: Lu W 

PROVIDER: S-EPMC5363825 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature