Cytotoxic T-lymphocyte-mediated killing of human pancreatic islet cells in vitro
- Author(s)
- Campbell, PD; Estella, E; Dudek, NL; Jhala, G; Thomas, HE; Kay, TWH; Mannering, SI;
- Details
- Publication Year 2008-09,Volume 69,Issue #9,Page 543-551
- Journal Title
- HUMAN IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- ELSEVIER SCIENCE INC
- Keywords
- NONOBESE DIABETIC MICE; BETA-CELLS; FAS LIGAND; GRANZYME-B; IFN-GAMMA; TNF-ALPHA; NOD MICE; EXPRESSION; INSULITIS; MELLITUS
- Publisher's Version
- https://doi.org/10.1016/j.humimm.2008.06.008
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2008-09-01 12:00:00