Gamma/delta T-cell functional responses differ after pathogenic human immunodeficiency virus and nonpathogenic simian immunodeficiency virus infections

The objective of this study was to functionally assess gamma/delta (gamma delta) T cells following pathogenic human immunodeficiency virus (HIV) infection of humans and nonpathogenic simian immunodeficiency virus (SIV) infection of sooty mangabeys. gamma delta T cells were obtained from peripheral blood samples from patients and sooty mangabeys that exhibited either a CD4-healthy (> 200 CD4(+) T cells/mu l blood) or CD4-low (< 200 CD4 cells/mu l blood) phenotype. Cytokine flow cytometry was utilized to assess production of Th1 cytokines tumor necrosis factor alpha and gamma interferon following ex vivo stimulation with either phorbol myristate acetate/ionomycin or the V delta 2 gamma delta T-cell receptor agonist isopentenyl pyrophosphate. Sooty mangabeys were observed to have higher percentages of gamma delta T cells in their peripheral blood than humans did. Following stimulation, gamma delta T cells from SIV-positive (SIV+) mangabeys maintained or increased their ability to express the Th1 cytokines regardless of CD4(+) T-cell levels. In contrast, HIV-positive (HIV+) patients exhibited a decreased percentage of gamma delta T cells expressing Th1 cytokines following stimulation. This dysfunction is primarily within the V delta 2(+) gamma delta T-cell subset which incurred both a decreased overall level in the blood and a reduced Th1 cytokine production. Patients treated with highly active antiretroviral therapy exhibited a partial restoration in their gamma delta T-cell Th1 cytokine response that was intermediate between the responses of the uninfected and HIV+ patients. The SIV+ sooty mangabey natural hosts, which do not proceed to clinical AIDS, provide evidence that gamma delta T-cell dysfunction occurs in HIV+ patients and may contribute to HIV disease progression.