Phenotypic and functional characterization of HIV-1-specific CD4 ⁺CD8 ⁺ double-positive T cells in early and chronic HIV-1 infection

OBJECTIVE:: CD4CD8 double-positive (DP) T cells represent a poorly characterized population of effector T cells found at low frequencies in the peripheral blood. Virus-specific DP T cells have been identified in HIV-1-infected patients but their origin, relationship to conventional CD4 and CD8 single-positive (SP) T cells, and role in disease pathogenesis are unclear. METHODS:: In this study, peripheral blood T cells were analyzed for cytokine production, maturation, and cytolytic marker expression by polychromatic flow cytometry in subjects with both early (n ≤ 27) and chronic (n ≤ 21) HIV-1 infection. RESULTS AND CONCLUSIONS:: HIV-1-specific interferon gamma (IFN-3)-producing DP T cells were identified at a median frequency of 0.48% compared with 1.08% and 0.02% for CD8 and CD4 SP cells, respectively, in response to pooled HIV-1 peptides. HIV-1-specific DP T cells exhibited polyfunctionality with characteristics of both CD4 and CD8 SP T cells, including coproduction of IFN- 3 and IL-2 and expression of cytolytic-associated lysosomal-associated membrane protein. No differences in frequencies of unstimulated DP T cells were observed in early compared with chronic infection. However, chronic infection was associated with higher frequencies of HIV-specific, IFN-3-producing DP T cells and higher fractions of effector memory and lysosomal-associated membrane protein expression among these cells, suggesting an effect of cumulative viral antigen burden on DP T-cell function.