CHANGES IN EXPRESSION OF SIGNAL-TRANSDUCTION PROTEINS IN T-LYMPHOCYTES OF PATIENTS WITH LEPROSY

Advanced stages of mycobacterial diseases such as leprosy and tubercul osis are characterized by a loss of T-cell function. The basis of this T-cell dysfunction is not well understood. The present report demonst rates major alterations in the expression of signal transduction molec ules in T cells of leprosy patients. These alterations were most frequ ently observed in lepromatous leprosy (LL) patients. Of 29 LL patients , 69% had decreased T-cell receptor zeta-chain expression, 48% had dec reased p56(lck) tyrosine kinase, and 63% had a loss of nuclear transcr iption factor NF-kappa B p65. An electrophoretic mobility shift assay with the gamma interferon core promoter region revealed a loss of the Th1 DNA-binding pattern in LL patients. In contrast, tuberculoid lepro sy patients had only minor signal transduction alterations. These nove l findings might improve our understanding of the T-cell dysfunction o bserved in leprosy and other infectious diseases and consequently migh t lead to better immunologic evaluation of patients.