T-cell release of granulysin contributes to host defense in leprosy.
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.
Ochoa
M T
MT
Division of Dermatology, University of California at Los Angeles School of Medicine, Los Angeles, California, USA.
Stenger
S
S
Sieling
P A
PA
Thoma-Uszynski
S
S
Sabet
S
S
Cho
S
S
Krensky
A M
AM
Rollinghoff
M
M
Nunes Sarno
E
E
Burdick
A E
AE
Rea
T H
TH
Modlin
R L
RL
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
D000890:Anti-Infective Agents; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; C075005:GNLY protein, human