title: T-cell release of granulysin contributes to host defense in leprosy.
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.
authors.affiliation: Division of Dermatology, University of California at Los Angeles School of Medicine, Los Angeles, California, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Ochoa
authors.forename: S
authors.initials: S
authors.lastname: Stenger
authors.forename: P A
authors.initials: PA
authors.lastname: Sieling
authors.forename: S
authors.initials: S
authors.lastname: Thoma-Uszynski
authors.forename: S
authors.initials: S
authors.lastname: Sabet
authors.forename: S
authors.initials: S
authors.lastname: Cho
authors.forename: A M
authors.initials: AM
authors.lastname: Krensky
authors.forename: M
authors.initials: M
authors.lastname: Rollinghoff
authors.forename: E
authors.initials: E
authors.lastname: Nunes Sarno
authors.forename: A E
authors.initials: AE
authors.lastname: Burdick
authors.forename: T H
authors.initials: TH
authors.lastname: Rea
authors.forename: R L
authors.initials: RL
authors.lastname: Modlin
mesh_terms: D000890:Anti-Infective Agents / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000276:immunology*; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D015440:Leprosy, Lepromatous / Q000276:immunology* / Q000473:pathology; D015441:Leprosy, Tuberculoid / Q000276:immunology* / Q000473:pathology
chemical_list: D000890:Anti-Infective Agents; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; C075005:GNLY protein, human