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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

157 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 - 2001

Funding

Acknowledgments This work was supported in part by grants from the National Institutes of Health (AI 22553, AR 40312, AI 07118, Al 43349). M.T.O. is a recipient of a fellowship from the Heiser Foundation. S.S. is supported by the AIDS Stipendium, Deutsches Krebsforschungszentrum Heidelberg and the German Research Foundation (SFB 263).

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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