Volume 9 Supplement 2
HIV-specific cytolytic CD4 T-cell responses effectively control HIV infection in macrophages
© Soghoian et al; licensee BioMed Central Ltd. 2012
Published: 13 September 2012
HIV-specific cytolytic CD4 T-cell responses expand during acute HIV infection in individuals who control viremia and are associated with better disease outcome. Up to 75% of the HIV-specific CD4 T-cells exhibit a cytolytic phenotype during acute infection, but it is not understood how cytolytic CD4 T-cells contribute to viral control or what their primary target cells are.
Using a novel, fluorescence-based single-round viral suppression assay, we assessed the ability of CD4 T-cells from HIV infected subjects to lyse infected macrophages. Elimination of infected macrophages and CD4 cytolytic phenotype were determined by flow cytometry. In addition, HIV-specific CD4 T-cell clones were generated and their cytolytic ability examined by Cr51-release and viral inhibition assays.
We observed significantly higher degranulatory HIV-specific CD4 T-cell responses in HIV controllers compared to progressors (p=0.015). Moreover, about 1/4 of all HIV-specific CD4 T-cell clones showed cytolytic activity by Cr51-release. Using a single-round viral suppression assay, we additionally observed that HIV-specific CD4 T-cells from chronically infected subjects were able to significantly lyse HIV infected macrophages (p=0.004). Elimination of HIV-infected macrophages was dose-dependent, up to 37% at E:T=5:1. Lytic ability could be observed ex vivo, and was enhanced after short term Gag-specific expansion in culture (11% to 32%, p=0.014). Furthermore, we observed that the inhibitory capacity of CD4 T cells could be abrogated using an HLA-DR blocking antibody. CD4 T-cell-mediated macrophage lysis was associated with strong HIV-specific cytolytic activity by intracellular cytokine staining and high expression of granzymes/perforin within HIV-specific CD4 T-cells.
Our data demonstrate that HIV-specific CD4 T-cells derived from infected individuals have the ability to eliminate infected macrophages. These data suggest a role for HIV-specific cytolytic CD4 T-cell responses, in the absence of CD8 T cell responses, in the lysis of HIV-infected macrophages, which represent important reservoirs for viral infection and viral dissemination.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.