Live attenuated lentivirus infection elicits polyfunctional simian immunodeficiency virus Gag-specific CD8+ T cells with reduced apoptotic susceptibility in rhesus macaques that control virus replication after challenge with pathogenic SIVmac239.
HIV-specific CD8+ T cells that secrete multiple cytokines in response to Ag stimulation are associated with the control of virus replication during chronic HIV infection. To determine whether the presence of polyfunctional CD8+ T cell responses distinguishes protected and unprotected monkeys in a live attenuated lentivirus model, SIV Gag peptide-specific CD8+ T cell responses of simian HIV (SHIV) 89.6-vaccinated, SIVmac239-challenged rhesus macaques were compared in two monkeys that controlled challenge virus replication and two that did not. The ratio of Bcl-2+ Gag-specific CD8+ T cells to caspase-3+ Gag-specific CD8+ T cells was higher in the vaccinated-protected animals compared with unprotected monkeys. In addition, polyfunctional SIV-specific CD8+ T cells were consistently detected through 12 wk postchallenge in the protected animals but not in the unprotected animals. In the unprotected monkeys, there was an increased frequency of CD8+ T cells expressing markers associated with effector memory T cells. Further, there was increased annexin V expression in central memory T cells of the unprotected animals before challenge. Thus, monkeys that control viral replication after live attenuated SHIV infection have polyfunctional SIV-specific CD8+ T cells with an increased survival potential. Importantly, the differences in the nature of the SIV-specific CD8+ T cell response in the protected and unprotected animals are present during acute stages postchallenge, before different antigenic levels are established. Thus, the polyfunctional capacity and increased survival potential of CD8+ SIV-specific T cells may account for live attenuated, SHIV89.6-mediated protection from uncontrolled SIV replication.
Genescà
Meritxell
M
Center for Comparative Medicine, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Rourke
Tracy
T
Li
Jun
J
Bost
Kristen
K
Chohan
Barinderpaul
B
McChesney
Michael B
MB
Miller
Christopher J
CJ
D000818:Animals; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004198:Disease Susceptibility; D015683:Gene Products, gag / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D016180:Lentivirus Infections / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008253:Macaca mulatta / Q000276:immunology* / Q000821:virology; D008297:Male; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012328:RNA Viruses / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000737:chemistry / Q000276:immunology* / Q000472:pathogenicity*; D014779:Virus Replication
D015683:Gene Products, gag; D019253:Proto-Oncogene Proteins c-bcl-2