CYTOKINE PATTERNS AT THE SITE OF MYCOBACTERIAL INFECTION

Distinct patterns of T cell cytokine production have been shown to inf luence the outcome of infection in mouse models and humans. Th1 or Typ e 1 cytokines, interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) a re generally associated with resistance to infection, whereas Th2 or T ype 2 cytokines, IL-4 and IL-10 are associated with progressive diseas e. Leprosy is a useful model for studying the role of cytokines in mod ulating T cell responses in human infectious disease. Infection by Myc obacterium lep,de results in disease manifestations that encompass an immunological spectrum. Tuberculoid patients are able to restrict the growth of the pathogen and mount strong T cell responses to M. leprae. In contrast, lepromatous patients manifest disseminated infection and their T cells weakly respond to M. leprae. We have found that tubercu loid leprosy lesions have a predominance of CD4(+) T cells producing t he Type 1 cytokine pattern. Secondly, IL-12 mRNA was expressed at 10-f old higher levels in tuberculoid lesions as compared to lepromatous le sions and that IL-12 promotes the selective expansion of the Type 1 cy tokine producing cells. In contrast, lepromatous lesions contain CD8() IL-4-producing cells that suppress antigen-specific T cell responses and promote the outgrowth of additional suppressor T cells. IL-10, al so expressed at higher levels in lepromatous as compared to tuberculoi d lesions, was found to be produced by macrophages, effectively inhibi ting cytokine production and macrophage activity.