PMID- 15041157
OWN - NLM
STAT- MEDLINE
DCOM- 20041110
LR  - 20121115
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 65
IP  - 3
DP  - 2004 Mar
TI  - Pathway of apoptosis induced in Jurkat T lymphoblasts by anti-HLA class I 
      antibodies.
PG  - 189-99
AB  - We demonstrated recently that human leukocyte antigen (HLA) class I human 
      monoclonal antibodies (mAbs) are able to induce apoptosis of resting human 
      lymphocytes as well as Jurkat lymphoblastic T cells. We now analyzed the 
      signaling pathway involved in apoptosis mediated by human HLA class I 
      allele-specific mAb OK2F3 and mouse monomorphic mAb W6/32. An inhibitor of a 
      broad spectrum of caspases had only a moderate inhibiting effect, and an 
      inhibitor of caspase 3 failed to inhibit HLA class I-mediated apoptosis. Although 
      caspase 3 activation was not observed, internucleosomal DNA fragmentation was 
      found in half of the apoptotic cells. Importantly, the mitochondrio-nuclear 
      redistribution of apoptosis inducing factor (AIF), a caspase-independent 
      mitochondrial death effector, was detected after 1 hour of treatment with human 
      anti-HLA mAb and was associated with large-scale DNA fragmentation, whereas the 
      release of cytochrome c, which is responsible for caspase-dependent 
      internucleosomal fragmentation, followed AIF translocation and occurred after 2 
      hours. Our results indicate that apoptosis mediated through HLA class I molecules 
      represents a unique mechanism of cell death in Jurkat T lymphoblasts that 
      involves two parallel pathways, one caspase-independent and the other 
      caspase-dependent. This study clarifies the precise mechanism of anti-HLA 
      antibody-induced apoptosis which might have clinical implications.
FAU - Daniel, Dinara
AU  - Daniel D
AD  - Department of Transplantation Immunology, Institute of Immunology, University of 
      Heidelberg, Heidelberg, Germany.
FAU - Opelz, Gerhard
AU  - Opelz G
FAU - Mulder, Arend
AU  - Mulder A
FAU - Kleist, Christian
AU  - Kleist C
FAU - Susal, Caner
AU  - Susal C
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (HLA Antigens)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/*physiology
MH  - Caspase 3
MH  - Caspase Inhibitors
MH  - Caspases/*metabolism
MH  - DNA Fragmentation
MH  - Enzyme Inhibitors/pharmacology
MH  - HLA Antigens/*pharmacology
MH  - Humans
MH  - Jurkat Cells
MH  - Membrane Potentials/drug effects/physiology
MH  - Mice
MH  - Mitochondria/*metabolism
MH  - Signal Transduction/physiology
EDAT- 2004/03/26 05:00
MHDA- 2004/11/13 09:00
CRDT- 2004/03/26 05:00
PHST- 2003/08/12 00:00 [received]
PHST- 2003/12/10 00:00 [revised]
PHST- 2003/12/12 00:00 [accepted]
PHST- 2004/03/26 05:00 [pubmed]
PHST- 2004/11/13 09:00 [medline]
PHST- 2004/03/26 05:00 [entrez]
AID - S019888590300661X [pii]
AID - 10.1016/j.humimm.2003.12.003 [doi]
PST - ppublish
SO  - Hum Immunol. 2004 Mar;65(3):189-99. doi: 10.1016/j.humimm.2003.12.003.