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Article
Nature Medicine  7, 174 - 179 (2001)
doi:10.1038/84620

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

Maria-Teresa Ochoa1, 9, Steffen Stenger4, Peter A. Sieling1, Sybille Thoma-Uszynski1, Shereen Sabet1, Sungae Cho1, Alan M. Krensky5, Martin Rollinghoff4, Euzenir Nunes Sarno6, Anne E. Burdick7, Thomas H. Rea8 & Robert L. Modlin1, 2, 3

1  Division of Dermatology, University of California at Los Angeles School of Medicine, Los Angeles, California, USA

2  Department of Microbiology and Immunology, University of California at Los Angeles School of Medicine, Los Angeles, California, USA

3  Molecular Biology Institute, University of California at Los Angeles School of Medicine, Los Angeles, California, USA

4  Institute for Clinical Microbiology, Immunology and Hygiene, Universität Erlangen, Erlangen, Germany

5  Division of Immunology and Transplantation Biology, Deptartment of Pediatrics, Stanford University, Stanford, California, USA

6  Leprosy Laboratory Institute Oswaldo Cruz, Rio de Janeiro - RJ/Brasil

7  Department of Dermatology and Cutaneous Surgery, University of Miami, Miami, Florida, USA

8  Section of Dermatology, and University of Southern California School of Medicine, Los Angeles, California, USA

9  International Center for Medical Research and Training (CIDEIM), Cali, Colombia

10  M.-T.O., S.S. and P.A.S. contributed equally to this study.

Correspondence should be addressed to Robert L. Modlin rmodlin@mednet.ucla.edu
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.

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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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