Expression of the IL-12 receptor beta 1 and beta 2 subunits in human tuberculosis

To determine whether the Th1 response in tuberculosis correlated with IL-12 R expression, we measured expression of the IL-12R beta 1 and IL-12R beta 2 subunits, as well as IL-12R beta 2 mRNA expression in tuberculosis patient s and healthy tuberculin reactors. In tuberculosis patients, IFN-gamma prod uction by Mycobacterium tuberculosis-stimulated PBMC was reduced, the perce ntages of T cells expressing IL-12R beta 1 and IL-12R beta 2 were significa ntly decreased, and IL-12R beta 2 mRNA expression was also markedly reduced . In contrast, in pleural fluid and lymph nodes at the site of disease in t uberculosis patients, in which IFN-gamma production is enhanced, IL-12R bet a 2 mRNA expression was also increased. In M. tuberculosis-stimulated perip heral blood T cells from tuberculosis patients, anti-IL-10 and anti-TGF-bet a enhanced IL-12R beta 1 and IL-12R beta 2 expression, and IFN-gamma produc tion. In M, tuberculosis-stimulated peripheral blood T cells from healthy t uberculin reactors, recombinant IL-10 and TGF-beta reduced IL-12R beta 1 an d IL-12R beta 2 expression, as well as IFN-gamma production, In combination with prior studies showing increased production of TGF-beta by blood monoc ytes from tuberculosis patients, this suggests that increased TGF-P product ion is the underlying abnormality that reduces IL-12R beta 1 and IL-12R bet a 2 expression in tuberculosis. Our findings provide evidence that IL-12R e xpression correlates well with IFN-gamma production in human tuberculosis, and that expression of IL-12R beta 1 and IL-12R beta 2 may play a central r ole in mediating a protective Th1 response.