The in vitro induction of human immunodeficiency virus (HIV) replication in purified protein derivative-positive HIV-infected persons by recall antigen response to Mycobacterium tuberculosis is the result of a balance of the effects of endogenous interleukin-2 and proinflammatory and antiinflammatory cytokines.
Coinfection with Mycobacterium tuberculosis and human immunodeficiency virus (HIV) is a serious problem, particularly in developing countries. Recently, M. tuberculosis and purified protein derivative (PPD) were demonstrated to induce HIV replication in CD8 T cell-depleted peripheral blood mononuclear cells from HIV-positive, PPD-positive persons but not in cells from PPD-negative persons. The role of endogenous and exogenous cytokines in modulating M. tuberculosis-induced HIV replication was evaluated. M. tuberculosis-induced HIV replication decreased following simultaneous inhibition of endogenous interleukin (IL)-2, IL-1beta, and tumor necrosis factor-alpha by the addition of soluble receptors and receptor antagonists or following exogenous IL-10 and transforming growth factor (TGF)-beta. In contrast, neutralization of endogenous IL-10 and TGF-beta augmented M. tuberculosis-induced HIV replication by increasing cellular activation. Thus, the balance between IL-2 and proinflammatory and antiinflammatory cytokines plays a major role in M. tuberculosis-induced replication of HIV.
Goletti
D
D
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-2520, USA.
Weissman
D
D
Jackson
R W
RW
Collins
F
F
Kinter
A
A
Fauci
A S
AS
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D006678:HIV / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008214:Lymphocytes / Q000276:immunology* / Q000821:virology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014373:Tuberculin / Q000276:immunology* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D016207:Cytokines; D016898:Interferon-alpha; D007378:Interleukins; D016212:Transforming Growth Factor beta; D014373:Tuberculin; D007371:Interferon-gamma