| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Center for Immunology, Departments of
Biochemistry, Molecular Biology and Biophysics, and
Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455.
Costimulation-dependent production and autocrine use of IL-2 by
activated CD8 T cells results in initial clonal expansion, but this is
transient. The cells quickly become anergic, unable to produce IL-2 in
response to Ag and costimulation, irrespective of the form of
costimulation. This activation-induced non-responsiveness (AINR)
differs from "classical" anergy in that it results despite the
cells receiving both signal 1 and signal 2. AINR cells can still
proliferate in response to exogenous IL-2, but can no longer produce
it. Other TCR-mediated events including cytolytic function and IFN-
production are not affected in the AINR state. To characterize the
mechanism(s) responsible for lack of IL-2 production in CD8 T cells in
the AINR state, microspheres bearing immobilized anti-TCR Abs or
peptide-MHC complexes, B7-1, and ICAM-1 were used to provide
well-defined stimuli to the cells. Comparison of normal and AINR cells
revealed that in AINR cells extracellular signal-regulated kinase
(ERK) is upregulated more transiently, Janus kinase activation
is substantially reduced, and activation of p38 is eliminated. PMA and
ionomycin restored proliferation and IL-2 production in AINR cells,
indicating a signaling defect upstream of Ras and protein kinase C.
Inhibitors of ERK (PD98059) and of p38 kinase (SB202190) blocked IL-2
mRNA expression and proliferation of both
peptide-MHC/B7-1/ICAM-1-stimulated normal cells and
PMA/ionomycin-stimulated AINR cells. Together these results demonstrate
that activation of at least ERK and p38 is essential for IL-2
production by CD8 T cells and that up-regulation of these
mitogen-activated protein kinases, along with Janus kinase, is
defective in AINR cells.
This article has been cited by other articles:
|
|
 |
|
  S. D. Liu, T. Tomassian, K. W. Bruhn, J. F. Miller, F. Poirier, and M. C. Miceli Galectin-1 Tunes TCR Binding and Signal Transduction to Regulate CD8 Burst Size J. Immunol., May 1, 2009; 182(9): 5283 - 5295. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Renda, S. Baraldo, G. Pelaia, E. Bazzan, G. Turato, A. Papi, P. Maestrelli, R. Maselli, A. Vatrella, L. M. Fabbri, et al. Increased activation of p38 MAPK in COPD Eur. Respir. J., January 1, 2008; 31(1): 62 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Horton, I. Frank, R. Baydo, E. Jalbert, J. Penn, S. Wilson, J. P. McNevin, M. D. McSweyn, D. Lee, Y. Huang, et al. Preservation of T Cell Proliferation Restricted by Protective HLA Alleles Is Critical for Immune Control of HIV-1 Infection J. Immunol., November 15, 2006; 177(10): 7406 - 7415. [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]
|
|
|
|
 |
|
 M. Uhlin, M. G. Masucci, and V. Levitsky Regulation of lck degradation and refractory state in CD8+ cytotoxic T lymphocytes PNAS, June 28, 2005; 102(26): 9264 - 9269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Y. Lin, T. Zal, I. L. Ch'en, N. R. J. Gascoigne, and S. M. Hedrick A Pivotal Role for the Multifunctional Calcium/Calmodulin-Dependent Protein Kinase II in T Cells: From Activation to Unresponsiveness J. Immunol., May 1, 2005; 174(9): 5583 - 5592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. L. Redmond, B. C. Marincek, and L. A. Sherman Distinct Requirements for Deletion versus Anergy during CD8 T Cell Peripheral Tolerance In Vivo J. Immunol., February 15, 2005; 174(4): 2046 - 2053. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Boissonnas, C. Combadiere, E. Lavergne, M. Maho, C. Blanc, P. Debre, and B. Combadiere Antigen Distribution Drives Programmed Antitumor CD8 Cell Migration and Determines Its Efficiency J. Immunol., July 1, 2004; 173(1): 222 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. F. Rowley and A. Al-Shamkhani Stimulation by Soluble CD70 Promotes Strong Primary and Secondary CD8+ Cytotoxic T Cell Responses In Vivo J. Immunol., May 15, 2004; 172(10): 6039 - 6046. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Mitchell and B. P. Lawrence Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Renders Influenza Virus-Specific CD8+ T Cells Hyporesponsive to Antigen Toxicol. Sci., July 1, 2003; 74(1): 74 - 84. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Curtsinger, D. C. Lins, and M. F. Mescher Signal 3 Determines Tolerance versus Full Activation of Naive CD8 T Cells: Dissociating Proliferation and Development of Effector Function J. Exp. Med., May 5, 2003; 197(9): 1141 - 1151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Myers, C. Takahashi, R. S. Mittler, R. J. Rossi, and A. T. Vella Effector CD8 T cells possess suppressor function after 4-1BB and Toll-like receptor triggering PNAS, April 29, 2003; 100(9): 5348 - 5353. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-X. Wang, B.-G. Chen, and G. E. Plautz Adoptive Immunotherapy of Advanced Tumors with CD62 L-Selectinlow Tumor-Sensitized T Lymphocytes Following Ex Vivo Hyperexpansion J. Immunol., September 15, 2002; 169(6): 3314 - 3320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Shrikant and M. F. Mescher Opposing Effects of IL-2 in Tumor Immunotherapy: Promoting CD8 T Cell Growth and Inducing Apoptosis J. Immunol., August 15, 2002; 169(4): 1753 - 1759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Tham and M. F. Mescher The Poststimulation Program of CD4 Versus CD8 T Cells (Death Versus Activation-Induced Nonresponsiveness) J. Immunol., August 15, 2002; 169(4): 1822 - 1828. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Tham, P. Shrikant, and M. F. Mescher Activation-Induced Nonresponsiveness: A Th-Dependent Regulatory Checkpoint in the CTL Response J. Immunol., February 1, 2002; 168(3): 1190 - 1197. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
