Location: Infectious Bacterial Diseases ResearchTitle: HIV-1 alters the cytokine microenvironment and effector function of CD8+T cells upon antigen-specific activation with mycobacteria Author
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 10/14/2012
Publication Date: 10/14/2012
Citation: Huante, M.B., Hogg, A.E., Devaraj, S.G., Cloyd, M.W., Graviss, E.A., Waters, W.R., Endsley, J.J. 2012. HIV-1 alters the cytokine microenvironment and effector function of CD8+T cells upon antigen-specific activation with mycobacteria [abstract]. Vaccine Conference and ISV Annual Global Congress. p. 22. Interpretive Summary:
Technical Abstract: Tuberculosis is the most common opportunistic infection in individuals living with human immunodeficiency virus (HIV). In addition to CD4+ T cell depletion, HIV infection compromises the function of CD8+ T cell-mediated immunity to Mycobacterium tuberculosis (M.tb). These effects on susceptibility to opportunistic pathogens like M.tb are poorly characterized, but are thought to correspond with defects in the common g chain cytokine networks in people with HIV-induced immune compromise. In this study, peripheral blood mononuclear cells (PBMC) from tuberculin-reactive donors and an in vitro system were used to determine the effects of HIV-1 (strain 213, T tropic) infection of CD4+ T cells on the CD8+ T cell memory response to mycobacterial antigens. In vitro infection with HIV-1 resulted in decreased antigen-specific CD8+ T cell proliferation, IFN-g and granulysin expression, as well as reduced antibacterial activity against mycobacteria-infected macrophages. Surprisingly, these effects were observed in the absence of differences in common g chain cytokine receptor expression on T cells due to HIV. To further identify the basis for reduced antigen-specific activation due to HIV, Bio-Plex ELISA was used to measure changes in the cytokine microenvironment. Infection of CD4+ T cells with HIV resulted in both general increases (IL-2, IL-10, VEGF) and decreases (IL-13, IL-5) of cytokine levels compared to mock-infected controls regardless of activation stimuli. A large number of cytokines increased over baseline values when stimulated with specific antigen (PPD, M. bovis BCG) or positive stimuli (IL-15, CD3/CD28). Interestingly, infection with HIV selectively reduced expression of several cytokines (IL-9, G-CSF, IFN-g, and TNF-a) dependent on choice of activation stimuli. These findings suggest differences in T cell activation pathways in terms of susceptibility to HIV-induced immune suppression, and could potentially lead to avenues to augment or restore antibacterial CD8+ T cell function in HIV+ patients.