Document Detail

Inhibition of caspase or FADD function blocks proliferation but not MAP kinase-activation and interleukin-2-production during primary stimulation of T cells.
MedLine Citation:
PMID:  12115619     Owner:  NLM     Status:  MEDLINE    
Caspases are instrumental in the implementation of apoptotic cell death, and caspase activation is in most investigated cases closely linked to apoptosis. Recent data demonstrate, however, that caspases are also activated during primary T cell activation in the absence of apoptosis. Here we provide evidence that caspase activity is required for some but not all aspects of T cell activation. CD3-triggered proliferation of mouse T cells was impaired in the presence of the pan-caspase-inhibitor Z-Val-Ala-Asp-fluoromethylketone (Z-VAD-fmk) and the number of cells entering the cell cycle was reduced. Costimulation by CD28 or externally added interleukin-2 (IL-2) failed to rescue proliferation. Re-stimulation of pre-activated T cells, however, was not affected by Z-VAD-fmk. Intriguingly, CD3-induced production of IL-2 by primary T cells was not impaired in the presence of Z-VAD-fmk. Likewise, CD3-induced activation of mitogen-activated protein kinases was unaffected by Z-VAD-fmk and intracellular levels of inhibitory kappaBalpha were the same as in control cells. T cells transgenically expressing a dominant negative mutant of the caspase-adaptor Fas-associated molecule with death domain (FADD)/MORT1 displayed the same pattern of reaction, i.e. a reduced proliferative response but normal IL-2-production. These data show a distinct role of caspases during primaryT cell activation and provide evidence for a FADD-caspase-pathway not only in the induction of apoptosis but also of T cell proliferation.
Astrid Mack; Georg Häcker
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of immunology     Volume:  32     ISSN:  0014-2980     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-07-12     Completed Date:  2002-08-13     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1986-92     Citation Subset:  IM    
Institute of Medical Microbiology, Immunology and Hygiene, Technical University Munich, Munich, Germany.
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MeSH Terms
Adaptor Proteins, Signal Transducing*
Amino Acid Chloromethyl Ketones / pharmacology
Antigens, CD3 / immunology
Carrier Proteins / antagonists & inhibitors*
Caspases / antagonists & inhibitors*
Cell Division / drug effects
Cells, Cultured
Cysteine Proteinase Inhibitors / pharmacology
Enzyme Activation
Fas-Associated Death Domain Protein
Interleukin-2 / biosynthesis*,  pharmacology
Jurkat Cells
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases / immunology*,  metabolism
T-Lymphocytes / drug effects,  immunology*
p38 Mitogen-Activated Protein Kinases
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Amino Acid Chloromethyl Ketones; 0/Antigens, CD3; 0/Carrier Proteins; 0/Cysteine Proteinase Inhibitors; 0/FADD protein, human; 0/Fadd protein, mouse; 0/Fas-Associated Death Domain Protein; 0/Interleukin-2; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; EC Protein Kinase 1; EC Protein Kinase 3; EC Protein Kinases; EC Mitogen-Activated Protein Kinases; EC 3.4.22.-/Caspases

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