INTERLEUKIN-10 DOWN-REGULATES MYCOBACTERIUM TUBERCULOSIS-INDUCED TH1 RESPONSES AND CTLA-4 EXPRESSION

To characterize the mechanism by which interleukin 10 (IL-10) inhibits Th1 responses to intracellular pathogens, we evaluated the interactio n between IL-10 and Mycobacterium tuberculosis-induced gamma interfero n (IFN-gamma) production by peripheral blood mononuclear cells from pe rsons across the spectrum of tuberculous infection, M. tuberculosis-in duced IFN-gamma production was highest in healthy tuberculin reactors, intermediate in human immunodeficiency virus (HIV)-negative tuberculo sis patients, and lowest in HIV-infected tuberculosis patients. Neutra lizing antibodies to IL-10 increased IFN-gamma production in HIV-infec ted and HIV-negative tuberculosis patients by enhancing monocyte IL-12 production. Expression of the T-cell-costimulatory molecule CTLA-4 wa s depressed in M. tuberculosis-stimulated peripheral blood mononuclear cells from tuberculosis patients, and anti-IL-10 and IL-12 upregulate d expression of CTLA-4. These findings provide evidence that intracell ular pathogens can inhibit Th1 responses and downregulate expression o f specific costimulatory molecules.