Th1-Th2 Paradigm: Insights from Leprosy

The mechanism by which T cells and cytokines regulate immune processes in skin can be investigated by studying patients with leprosy. The disease, caused by the obligate intracellular bacterium Mycobacterium leprae, forms a spectrum. At one pole, patients with tuberculoid leprosy are able to restrict the growth of the pathogen and their skin lesions are characterized by a predominance of CD4+ T cells and type 1 cytokines including interleukin 2 and interferon gamma. At the opposite pole, patients with lepromatous leprosy are unable to contain the infection and their skin lesions are characterized by a predominance of CD8+ T cells and type 2 cytokines including interleukins 4 and 10. A key determinant of the T-cell cytokine response may be interleukin 12, which selectively favors expansion of CD4+ T cells producing interferon gamma. By understanding the factors that regulate T-cell and cytokine responses in leprosy, it should be possible to devise specific immunologic interventions in diseases of skin.