Immunopathogenesis of Leprosy: A Model for T Cell Anergy

Abstract

Leprosy is a model disease for understanding human immune responses underlying diseases caused by intracellular pathogens, as well as providing valuable insights into autoimmune disorders and cancer. This review addresses the unresponsiveness/anergy of host T cells to the causative pathogen Mycobacterium leprae and describes both the adaptive and innate immune responses observed during the clinical course of the disease. Leprosy presents as a clinicopathological spectrum, with divergence in antigen-specific T cell responses and antibodies in patients at the two ends of the spectrum. Tuberculoid leprosy at one end presents with localised hypopigmented paucibacillary skin patches, and shows effective antigen-specific T cell responses and low antibodies. In contrast, lepromatous leprosy at the other end presents with generalised lesions with bacillary proliferation, abundant antibodies, and T cell unresponsiveness/anergy to M. leprae. Recent advances that may explain clinical divergence and T cell unresponsiveness/anergy associated with lepromatous leprosy include: cytokine dysregulation, T helper (Th)1, Th2 paradigm, Th17 cells, FOXP3+ regulatory T cells, and pathogen-induced accessory cell subversion.