Abstract
Leprosy is a disease caused by an intracellular bacillus bacterium called Mycobacterium leprae which lives and multiplies in the hosts' macrophages and Schwann cells. Depending on the degree of the host's cell-mediated immunity (CMI) response to the bacilli, the disease manifests itself in five clinical spectra ranging from polar tuberculoid (TT) to polar lepromatous leprosy (LL). A very high level of T helper 1 (Th1) driven bacilli-specific CMI is seen in the TT form, whereas this response is essentially nonexistent in the LL form. As a result, there is very low or absent bacillary load and localized nodular lesions in TT patients. On the contrary, LL patients presented with high bacillary load and generalized lesions due to low CMI response. The mechanism underlying this divergence of CMI response is not clearly elucidated yet. However, mounting evidence links it to an elevated number of Th1 and Th17 suppressing CD4(+) CD25(+) FOXP3(+) T regulatory cells (Treg cells) which are abundantly found in LL than in TT patients. The predominance of these cells in LL patients is partly attributed to a deficiency of leptin, the cytokine-like peptide hormone, in these patients. Becausea normal level of leptin promotes the proliferation and preferential differentiation of effector T cells (Th1 and Th17) while inhibiting the growth and functional responsiveness of the Treg cells. In contrast, leptin deficiency or neutralization was reported to exert the opposite effect on Treg cells and effector T cells. Other smaller subsets of lymphocytes such as gamma delta (γδ) T cells and B regulatory cells are also modulated by leptin level in the pathogenesis of leprosy. Leptin may therefore regulate the divergence of CMI between TT and LL patients by regulating the homeostasis of effector T cells and Treg cells, and this review will examine the underlying mechanism for this.