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  • Title: Single-cell level response of HIV-specific and cytomegalovirus-specific CD4 T cells correlate with viral control in chronic HIV-1 subtype A infection.
    Author: Eller MA, Eller LA, Ratto-Kim S, Ouma BJ, Lo V, de Souza M, Guwatudde D, Nails B, Michael NL, Wabwire-Mangen F, Robb ML, Marovich MA, Sandberg JK, Currier JR.
    Journal: J Acquir Immune Defic Syndr; 2012 Sep 01; 61(1):9-18. PubMed ID: 22580564.
    Abstract:
    BACKGROUND AND OBJECTIVE: HIV-1 subtype A is the second most prevalent subtype globally and is associated with reduced viral load, higher CD4 absolute counts, and slower disease progression. To study the possible role of T cells associated with better outcome, we examined CD4 and CD8 T-cell responses against HIV-1 and cytomegalovirus (CMV) in Ugandans infected with subtype A HIV-1. METHODS: T-cell responses were investigated using flow cytometry and novel subtype A variant inclusive peptide (VIP) sets designed for this evaluation. CD4 T-cell responses focused primarily on Gag, whereas CD8 T-cell responses were broadly directed against Gag, gp41, and Nef VIP sets. CD4 T cells primarily responded with interferon (IFN)-γ, whereas CD8 cells were more diverse with degranulation (CD107a), IFN-γ, and macrophage inflammatory protein (MIP)-1β production. RESULTS: No relationship was observed between CD8 T-cell responses and the HIV-1 load. Similarly, the frequency of CD4 T cells responding to these antigens did not associate with viral control. However, in CD4 T cells responding against Gag or CMV, the IFN-γ intensity, indicative of the production at the single-cell level, was inversely proportional to viral load. No significant relationship was found between T-cell effector/memory phenotype and viral control. CONCLUSIONS: The per cell production of IFN-γ in CD4 T cells responding to HIV-1 or CMV correlated with viral control in chronic HIV-1 subtype A infection. These data suggest that quantitative aspects at the single-cell level may be more important than the frequency of antigen-specific CD4 T cells in HIV-1 subtype A infection control.
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