期刊
HUMAN IMMUNOLOGY
卷 69, 期 9, 页码 543-551出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.humimm.2008.06.008
关键词
cytotoxic T; lymphocytes; diabetes; perforin; MHC class 1; transplantation
类别
资金
- Juvenile Diabetes Research Foundation
- Australian Government
- National Health and Medical Research Council of Australia
Cytotoxic T lymphocytes (CTL) are believed to play an essential role in P-cell destruction leading to development of type 1 diabetes and allogeneic islet graft failure. We aimed to identify the mechanisms used by CTL to kill human 0 cells. CTL clones that recognize epitopes from influenza virus and Epstein-Barr virus restricted by human leukocyte antigen (HLA)-A0201 and -B0801, respectively, were used to investigate the susceptibility of human 0 cells to CTL. In a short-term (5-hour) assay, CTL killed human islet cells of the appropriate major histocompatibility complex (MHC) class I type that had been pulsed with viral peptides. Killing was increased by pretreating islets with interferon gamma that increases MHC class I on target cells. Killing was abolished by incubation of CTL with the perforin inhibitor concanamycin A. The Fas pathway did not contribute to killing because blocking with neutralizing anti-Fas ligand antibody did not significantly reduce beta-celt killing. In conclusion, we report a novel way of investigating the interaction between CTL and human islets. Human islets were rapidly killed in vitro by MHC class I-restricted CTL predominantly by the granule exocytosis pathway. (C) 2008 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
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