| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
* Immunology and
Experimental Pathology, Holland Laboratory, American Red Cross, Rockville, MD 20855; and
Department of Immunology, Institute for Biological Sciences, George Washington University, Washington, DC 20037
Short-term culture of activated T cells with IL-2 renders them
highly susceptible to apoptotic death triggered by TCR cross-linking.
Activation-induced apoptosis is contingent upon caspase activation and
this is mediated primarily by Fas/Fas ligand (FasL) interactions that,
in turn, are optimized by p38 mitogen-activated protein kinase
(MAPK)-regulated signals. Although T cells from mice bearing mutations
in Fas (lpr) or FasL
(gld) are more resistant to activation-induced cell
death (AICD) than normal T cells, a significant proportion of
CD8+ T cells and to a lesser extent
CD4+ T cells from mutant mice die after TCR religation.
Little is known about this Fas-independent death process. In this
study, we demonstrate that AICD in lpr and
gld CD4+ and
CD8+ T cells occurs predominantly by a novel
mechanism that is TNF-
-, caspase-, and p38 MAPK-independent and has
morphologic features more consistent with oncosis/primary necrosis than
apoptosis. A related Fas- and caspase-independent, nonapoptotic death
process is revealed in wild-type (WT) CD8+ T
cell blasts following TCR ligation and treatment with caspase
inhibitors, the p38 MAPK inhibitor, SB203580, or neutralizing
anti-FasL mAb. In parallel studies with WT
CD4+ T cells, two minor pathways leading to
nonapoptotic, caspase-independent AICD were identified, one contingent
upon Fas ligation and p38 MAPK activation and the other Fas- and p38
MAPK-independent. These data indicate that TCR ligation can activate
nonapoptotic death programs in WT CD8+ and
CD8+ T blasts that normally are masked by
Fas-mediated caspase activation. Selective use of potentially
proinflammatory oncotic death programs by activated lpr
and gld T cells may be an etiologic factor in
autosensitization.
This article has been cited by other articles:
|
|
 |
|
  W. Li, S.-i. Kashiwamura, H. Ueda, A. Sekiyama, and H. Okamura Protection of CD8+ T cells from activation-induced cell death by IL-18 J. Leukoc. Biol., July 1, 2007; 82(1): 142 - 151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Woelfel, J. Bixby, M. A. Brehm, and F. K.-M. Chan Transgenic Expression of the Viral FLIP MC159 Causes lpr/gld-Like Lymphoproliferation and Autoimmunity J. Immunol., September 15, 2006; 177(6): 3814 - 3820. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kennedy and E. Celis T Helper Lymphocytes Rescue CTL from Activation-Induced Cell Death. J. Immunol., September 1, 2006; 177(5): 2862 - 2872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Milhas, O. Cuvillier, N. Therville, P. Clave, M. Thomsen, T. Levade, H. Benoist, and B. Segui Caspase-10 Triggers Bid Cleavage and Caspase Cascade Activation in FasL-induced Apoptosis J. Biol. Chem., May 20, 2005; 280(20): 19836 - 19842. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Nussbaum and J. L. Whitton The Contraction Phase of Virus-Specific CD8+ T Cells Is Unaffected by a Pan-Caspase Inhibitor J. Immunol., December 1, 2004; 173(11): 6611 - 6618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Wu, M. Roberts, M. Porter, F. Walker, E. J. Wherry, J. Kelly, M. Gadina, E. M. Silva, G. A. DosReis, M. F. Lopes, et al. Viral FLIP Impairs Survival of Activated T Cells and Generation of CD8+ T Cell Memory J. Immunol., May 15, 2004; 172(10): 6313 - 6323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wang, X. Li, L. Wang, P. Ding, Y. Zhang, W. Han, and D. Ma An alternative form of paraptosis-like cell death, triggered by TAJ/TROY and enhanced by PDCD5 overexpression J. Cell Sci., March 15, 2004; 117(8): 1525 - 1532. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
