Submitted to: Meeting Abstract
Publication Type: Abstract only
Publication Acceptance Date: 4/11/2011
Publication Date: 4/11/2011
Citation: Huante, M.B., Hogg, A.E., Deveraj, M.W., Cloyd, E.A., Graviss, W.R., Waters, W.R., Endsley, J.J. 2011. Infection of PBMC with HIV-1 impairs effector function of Mycobacteria-specific CD8+ T cells from tuberculin-reactive donors [abstract]. p. 1. Interpretive Summary:
Technical Abstract: Tuberculosis is the most common opportunistic infection in individuals living with human immunodeficiency virus (HIV). The HIV crisis has further aided in the development of multi- or extensively- drug resistant TB (MDR-, XDR-TB). In addition to CD4+ T cell depletion, HIV infection compromises the function of several other components of cell mediated immunity to Mycobacterium tuberculosis (M.tb). The effects of HIV on the antibacterial activity of CD8+ T cells against mycobacteria and other opportunistic pathogens however, are poorly characterized. In these studies we used primary human peripheral blood mononuclear cells (PBMC) and an in vitro system to determine the effects of HIV-1 (strain 213) on antigen-specific (memory) recall to PPD or BCG by peripheral blood CD8+ T cells of healthy tuberculin skin test positive individuals. Antigen-specific CD8+ T cell activation was assessed by using multivariate flow cytometry, ELISA, real time PCR, and a CFU reduction assay. Our results demonstrate that HIV-1 infection of PBMC suppresses antigen-specific activation of CD8+T cells, including proliferation, expression of IFN-g and granulysin, and contact-dependent antibacterial activity by CD8+ T cells against mycobacteria-infected macrophages. These in vitro effects were not associated with changes in the common gamma chain cytokines (IL-2, IL-7, IL-15, and IL-21) or the receptors as has been postulated as a cause for cytotoxic T cell dysfunction based on observations in HIV+ patients. These findings suggest that suppression of CD8+ T cell effector function could contribute to the increased susceptibility of HIV+ patients to M.tb infection and suggest a mechanism independent from disruption of common gamma chain cytokine networks. These results have important implications for the use of cytokine-based immunotherapy to augment or restore CD8+ T cell function in HIV+ patients to boost host defense to M.tb or other opportunistic pathogens.