Expression of transforming growth factor-beta isoforms and their receptors in lepromatous and tuberculoid leprosy

Leprosy is an infectious disease with two polar forms, tuberculoid leprosy (TT) and lepromatous leprosy (LL), that are characterized by strong cell-mediated immunity (CMI) and CMI anergy, respectively. Transforming growth factor-beta (TGF-beta) belongs to a family of pleiotropic cytokines (TGF-beta1, TGF-beta2 and TGF-beta3) that participate in the control of cell differentiation and proliferation, as well as tissue repair. This cytokine family is unique because it suppresses CMI. In this study, we compared the expression of the three TGF-beta isoforms and their receptors in skin biopsies from LL and TT patients (LL = 20; TT = 20) using immunohistochemistry and automated morphometry. The percentage of cells immunostained for the three TGF-beta isoforms and cells positive for the three TGF-beta receptors in the inflammatory infiltrate located in the papillary dermis, reticular dermis and periadnexal tissue were significantly higher in LL than that in TT, with macrophages being the most common and strongest immunoreactive cells. Some lymphocytes, fibroblasts, keratinocytes and epithelial cells from sweat glands and hair roots were also positive. In situ reverse-transcription polymerase chain reaction corroborated the capacity of these cells to synthesize TGF-beta1 and TGF-beta receptor 2. This high expression of TGF-beta isoforms and their receptors could contribute to CMI anergy and other clinical characteristic features of leprosy, like skin atrophy.