Journal
JOURNAL OF IMMUNOLOGY
Volume 179, Issue 7, Pages 4732-4740Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.179.7.4732
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Funding
- NCRR NIH HHS [P51 RR000169, RR00169] Funding Source: Medline
- NIAID NIH HHS [P01 AI066314-029001, P01 AI066314-04, P01 AI066314-02, P01 AI066314, P01 AI066314-020001, P01 AI066314-039001, P01 AI066314-01, P01 AI066314-03, P01 AI066314-04S1, P01 AI066314-030001, P01 AI066314-040001, P01 AI066314-049001, P01 AI066314-010001, P01 AI066314-019001, P01 AI066314-017490, R01 AI44480] Funding Source: Medline
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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, SIHV89.6-mediated protection from uncontrolled SIV replication.
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