Cytokine patterns at the site of mycobacterial infection

Abstract

Distinct patterns of T cell cytokine production have been shown to influence the outcome of infection in mouse models and humans. Th1 or Type 1 cytokines, interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) are generally associated with resistance to infection, whereas Th2 or Type 2 cytokines, IL-4 and IL-10 are associated with progressive disease. Leprosy is a useful model for studying the role of cytokines in modulating T cell responses in human infectious disease. Infection by Mycobacterium leprae 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 tuberculoid leprosy lesions have a predominance of CD4+ T cells producing the Type 1 cytokine pattern. Secondly, IL-12 mRNA was expressed at 10-fold higher levels in tuberculoid lesions as compared to lepromatous lesions and that IL-12 promotes the selective expansion of the Type 1 cytokine 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, also expressed at higher levels in lepromatous as compared to tuberculoid lesions, was found to be produced by macrophages, effectively inhibiting cytokine production and macrophage activity.