Transcriptional profiling of peripheral CD8+T cell responses to SIVδnef and SIVmac251 challenge reveals a link between protective immunity and induction of systemic immunoregulatory mechanisms

Michael D. George, William Hu, James M. Billingsley, R. Keith Reeves, Sumathi Sankaran-Walters, R. Paul Johnson, Satya Dandekar

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Immunization of macaques with attenuated simian immunodeficiency virus (SIV) with deletions in nef (SIVδnef) is shown to elicit protective immunity to infection by pathogenic SIV, yet the mechanisms that orchestrate protection and prevent pathogenesis remains unknown. We utilized whole-genome transcriptional profiling to reveal molecular signatures of protective immunity in circulating CD8+ T cells of rhesus macaques vaccinated with SIVmac239δnef and challenged with pathogenic SIVmac251. Our findings suggest that protective immunity to pathogenic SIV infection induced by SIVmac239δnef is associated with balanced induction of T cell activation and immunoregulatory mechanisms and dampened activation of interferon-induced signaling pathways and cytolytic enzyme production as compared with pathogenic SIVmac251 infection of unvaccinated controls. We provide evidence that protective immunity to SIVmac251 correlates with induction of biomarkers of T cell activation, differentiation, signaling, and adhesion that were down regulated in unvaccinated controls. The study highlights potential immunomodulatory networks associated with protective immunity against the virus.

Original languageEnglish (US)
Pages (from-to)581-591
Number of pages11
JournalVirology
Volume468
DOIs
StatePublished - Nov 1 2014

Keywords

  • CD8+T cell response
  • Gene expression
  • HIV
  • Immune activation
  • Immune regulation
  • Immunization
  • Microarray
  • SIV
  • Vaccine

ASJC Scopus subject areas

  • Virology

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