A role for IL-12 receptor expression and signal transduction in host defense in leprosy

The generation of cell-mediated immunity against intracellular infection in volves the production of IL-12, a critical cytokine required for the develo pment of Th1 responses. The biologic activities of IL-12 are mediated throu gh a specific, high affinity IL-12R composed of an 1L-12R beta1/IL-12R beta 2 heterodimer, with the IL-12R beta2 chain involved in signaling via Stat4. We investigated IL-12R expression and function in human infectious disease , using the clinical/immunologic spectrum of leprosy as a model. T cells fr om tuberculoid patients, the resistant form of leprosy, are responsive to I L-12; however, T cells from lepromatous patients, the susceptible form of l eprosy, do not respond to IL-12. We found that the IL-12R beta2 was more hi ghly expressed in tuberculoid lesions compared with lepromatous lesions. In contrast, IL-12R beta1 expression was similar in both tuberculoid and lepr omatous lesions. The expression of IL-12R beta2 on T cells was up-regulated by Mycobacterium leprae in tuberculoid but not in lepromatous patients. Fu rthermore, IL-12 induced Stat4 phosphorylation and DNA binding in M. leprae -activated T cells from tuberculoid but not from lepromatous patients. Inte restingly, IL-12R beta2 in lepromatous patients could be up-regulated by st imulation with M. tuberculosis. These data suggest that Th response to M. l eprae determines IL-12R beta2 expression and function in host defense in le prosy.