PMID- 18639598
OWN - NLM
STAT- MEDLINE
DCOM- 20081114
LR  - 20081121
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 69
IP  - 9
DP  - 2008 Sep
TI  - Cytotoxic T-lymphocyte-mediated killing of human pancreatic islet cells in vitro.
PG  - 543-51
LID - 10.1016/j.humimm.2008.06.008 [doi]
AB  - Cytotoxic T lymphocytes (CTL) are believed to play an essential role in beta-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 beta 
      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 beta 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-cell 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.
FAU - Campbell, Peter D
AU  - Campbell PD
AD  - St Vincent's Institute, The University of Melbourne Department of Medicine, St. 
      Vincent's Hospital, Fitzroy, Australia.
FAU - Estella, Eugene
AU  - Estella E
FAU - Dudek, Nadine L
AU  - Dudek NL
FAU - Jhala, Gaurang
AU  - Jhala G
FAU - Thomas, Helen E
AU  - Thomas HE
FAU - Kay, Thomas W H
AU  - Kay TW
FAU - Mannering, Stuart I
AU  - Mannering SI
LA  - eng
PT  - Journal Article
DEP - 20080717
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (HLA Antigens)
RN  - 0 (Macrolides)
RN  - 126465-35-8 (Perforin)
RN  - 80890-47-7 (concanamycin A)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Cell Line, Tumor
MH  - Clone Cells/drug effects/*immunology/metabolism
MH  - *Cytotoxicity, Immunologic
MH  - Epitopes, T-Lymphocyte/*immunology/metabolism
MH  - Fas Ligand Protein/immunology/metabolism
MH  - HLA Antigens/immunology/metabolism
MH  - Humans
MH  - Interferon-gamma/pharmacology
MH  - Islets of Langerhans/*immunology/metabolism
MH  - Macrolides/pharmacology
MH  - Perforin/immunology/metabolism
MH  - T-Lymphocytes, Cytotoxic/immunology/*metabolism
EDAT- 2008/07/22 09:00
MHDA- 2008/11/15 09:00
CRDT- 2008/07/22 09:00
PHST- 2008/05/02 00:00 [received]
PHST- 2008/06/10 00:00 [revised]
PHST- 2008/06/16 00:00 [accepted]
PHST- 2008/07/22 09:00 [pubmed]
PHST- 2008/11/15 09:00 [medline]
PHST- 2008/07/22 09:00 [entrez]
AID - S0198-8859(08)00108-0 [pii]
AID - 10.1016/j.humimm.2008.06.008 [doi]
PST - ppublish
SO  - Hum Immunol. 2008 Sep;69(9):543-51. doi: 10.1016/j.humimm.2008.06.008. Epub 2008 
      Jul 17.