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

被引:135
作者
Ochoa, MT
Stenger, S
Sieling, PA
Thoma-Uszynski, S
Sabet, S
Cho, SG
Krensky, AM
Rollinghoff, M
Sarno, EN
Burdick, AE
Rea, TH
Modlin, RL [1 ]
机构
[1] Univ Calif Los Angeles, Sch Med, Dept Microbiol & Immunol, Div Dermatol, Los Angeles, CA 90024 USA
[2] Univ Calif Los Angeles, Sch Med, Inst Mol Biol, Los Angeles, CA 90024 USA
[3] Univ Erlangen Nurnberg, Inst Clin Microbiol Immunol & Hyg, Erlangen, Germany
[4] Stanford Univ, Dept Pediat, Div Immunol & Transplantat Biol, Stanford, CA 94305 USA
[5] Inst Oswaldo Cruz, Leprosy Lab, BR-20001 Rio De Janeiro, Brazil
[6] Univ Miami, Dept Dermatol & Cutaneous Surg, Miami, FL 33152 USA
[7] Univ So Calif, Sch Med, Los Angeles, CA USA
[8] Univ So Calif, Dermatol Sect, Los Angeles, CA USA
[9] Int Ctr Med Res & Training CIDEIM, Cali, Colombia
关键词
D O I
10.1038/84620
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:174 / 179
页数:6
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