T-cell release of granulysin contributes to host defense in leprosy

A novel mechanism by which T cells contribute to host defense against micro bial pathogens is release of the antimicrobial protein granulysin. We inves tigated the role of granulysin in human infectious disease using leprosy as a model. Granulysin-expressing T cells were detected in cutaneous leprosy lesions at a six-fold greater frequency in patients with the localized tube rculoid as compared with the disseminated lepromatous form of the disease. In contrast, perforin, a cytolytic molecule that colocalizes with granulysi n in cytotoxic granules, was expressed at similar levels across the spectru m of disease. Within leprosy lesions, granulysin colocalized in CD4(+) T ce lls and was expressed in CD4(+) T-cell lines derived from skin lesions. The se CD4(+) T-cell lines lysed targets by the granule exocytosis pathway and reduced the viability of mycobacteria in infected targets. Given the broad antimicrobial spectrum of granulysin, these data provide evidence that T-ce ll release of granulysin contributes to host defense in human infectious di sease.