title: 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.
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 SIVmac239∆nef 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.
authors.affiliation: Department of Medical Microbiology and Immunology, University of California, Davis, Davis, CA, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: George
authors.affiliation: Department of Medical Microbiology and Immunology, University of California, Davis, Davis, CA, United States.
authors.forename: William
authors.initials: W
authors.lastname: Hu
authors.affiliation: Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, MA, United States.
authors.forename: James M
authors.initials: JM
authors.lastname: Billingsley
authors.affiliation: Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, MA, United States.
authors.forename: R Keith
authors.initials: RK
authors.lastname: Reeves
authors.affiliation: Department of Medical Microbiology and Immunology, University of California, Davis, Davis, CA, United States.
authors.forename: Sumathi
authors.initials: S
authors.lastname: Sankaran-Walters
authors.affiliation: Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, MA, United States.
authors.forename: R Paul
authors.initials: RP
authors.lastname: Johnson
authors.affiliation: Department of Medical Microbiology and Immunology, University of California, Davis, Davis, CA, United States. Electronic address: sdandekar@ucdavis.edu.
authors.forename: Satya
authors.initials: S
authors.lastname: Dandekar
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D008253:Macaca mulatta; D011956:Receptors, Cell Surface; D018449:SAIDS Vaccines / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D059467:Transcriptome; D019562:Viral Load
chemical_list: D011956:Receptors, Cell Surface; D018449:SAIDS Vaccines
keywords: CD8+T cell response; Gene expression; HIV; Immune activation; Immune regulation; Immunization; Microarray; SIV; Vaccine