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

PLoS One. 2017 Mar 23;12(3):e0173929. doi: 10.1371/journal.pone.0173929. eCollection 2017.

Abstract

The live attenuated vaccine (LAV) SIVmac239Δnef (SIVΔnef) 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 SIVΔnef, 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, TCRα, TCRβ, CD28 and decreased expression of CTLA-4, IFN-γ, RANTES, granzyme A and B. Our study suggests that a higher quality of SIV-specific CD8+ T cells elicited by SIVΔnef over time contributes to the maturation of time-dependent protection.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • Gene Products, gag / immunology*
  • Gene Products, nef / immunology
  • Immunity, Cellular
  • Immunity, Humoral
  • Macaca mulatta / immunology
  • Macaca mulatta / virology
  • Male
  • SAIDS Vaccines / immunology*
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / prevention & control*
  • Simian Immunodeficiency Virus / immunology*
  • Time Factors
  • Transcriptome*
  • Vaccines, Attenuated / immunology

Substances

  • Gene Products, gag
  • Gene Products, nef
  • SAIDS Vaccines
  • Vaccines, Attenuated