Transforming Growth Factor-β Suppresses Interleukin (IL)-2 and IL-1β Production in HIV-Tuberculosis Co-Infection.

Interleukin (IL)-1β and IL-2 play important roles in protective immune responses against Mycobacterium tuberculosis (Mtb) infection. Information on the factors that regulate the production of these cytokines in the context of human immunodeficiency virus and latent tuberculosis infection (LTBI) or active tuberculosis (TB) disease is limited. In this study, we compared the production of these cytokines by peripheral blood mononuclear cells (PBMCs) from HIV- and HIV+ individuals with latent and active Tuberculosis infection in response to Mtb Antigen 85A. PBMCs from HIV+ LTBI+ and HIV+ active TB patients produced low IL-1β, IL-2 but high transforming growth factor beta (TGF-β) compared to healthy controls. CD4+ T cells from HIV patients expressed low retinoic acid-related orphan receptor gamma (RORγ), and high suppressors of cytokine signaling-3 (SOCS-3). Active TB infection in HIV+ individuals further inhibited antigen-specific IL-1β and IL-2 production compared with those with LTBI. Neutralization of TGF-β restored IL-1β and IL-2 levels and lowered SOCS-3 production by CD4+ T cells. We hypothesize that high TGF-β in HIV patients could be a reason for defective Mtb-specific IL-1β, IL-2 production and activation of latent TB in HIV. Coupling anti-TGF-β antibodies with antiretroviral therapy treatment might increase T cell function to boost the immune system for effective clearance of Mtb.