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

Maria Teresa Ochoa, Steffen Stenger, Peter A. Sieling, Sybille Thoma-Uszynski, Shereen Sabet, Sungae Cho, Alan M. Krensky, Martin Rollinghoff, Euzenir Nunes Sarno, Anne E. Burdick, Thomas H. Rea, Robert L. Modlin

Research output: Contribution to journalArticle

136 Scopus citations

Abstract

A novel mechanism by which T cells contribute to host defense against microbial pathogens is release of the antimicrobial protein granulysin. We investigated 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 tuberculoid as compared with the disseminated lepromatous form of the disease. In contrast, perforin, a cytolytic molecule that colocalizes with granulysin in cytotoxic granules, was expressed at similar levels across the spectrum of disease. Within leprosy lesions, granulysin colocalized in CD4+ T cells and was expressed in CD4+ T-cell lines derived from skin lesions. These 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-cell release of granulysin contributes to host defense in human infectious disease.

Original languageEnglish (US)
Pages (from-to)174-179
Number of pages6
JournalNature medicine
Volume7
Issue number2
DOIs
StatePublished - Feb 22 2001

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Ochoa, M. T., Stenger, S., Sieling, P. A., Thoma-Uszynski, S., Sabet, S., Cho, S., Krensky, A. M., Rollinghoff, M., Nunes Sarno, E., Burdick, A. E., Rea, T. H., & Modlin, R. L. (2001). T-cell release of granulysin contributes to host defense in leprosy. Nature medicine, 7(2), 174-179. https://doi.org/10.1038/84620