| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Department of Immunology, University of Toronto, Toronto, Ontario, Canada; and
Department of Medical Biophysics, University of Toronto and Ontario Cancer Institute, Toronto, Ontario, Canada
4-1BB is a member of the TNFR superfamily expressed on activated CD4+ and CD8+ T cells. 4-1BB can costimulate IL-2 production by resting primary T cells independently of CD28 ligation. In this study, we report signaling events following 4-1BB receptor aggregation using an Ak-restricted costimulation-dependent T cell hybridoma, C8.A3. Aggregation of 4-1BB on the surface of C8.A3 cells induces TNFR-associated factor 2 recruitment, which in turn recruits and activates apoptosis signal-regulating kinase-1, leading to downstream activation of c-Jun N-terminal/stress-activated protein kinases (JNK/SAPK). 4-1BB ligation also enhances anti-CD3-induced JNK/SAPK activation in primary T cells. Overexpression of a catalytically inactive form of apoptosis signal-regulating kinase-1 in C8.A3 T cells interferes with activation of the SAPK cascade and with IL-2 secretion, consistent with a critical role for JNK/SAPK activation in 4-1BB-dependent IL-2 production. Given the ability of both CD28 and 4-1BB to induce JNK/SAPK activation, we asked whether hyperosmotic shock, another inducer of this cascade, could function to provide a costimulatory signal to T cells. Osmotic shock of resting primary T cells in conjunction with anti-CD3 treatment was found to costimulate IL-2 production by the T cells, consistent with a pivotal role for JNK/SAPK in T cell costimulation.
This article has been cited by other articles:
|
|
 |
|
  L. Sabbagh, G. Pulle, Y. Liu, E. N. Tsitsikov, and T. H. Watts ERK-Dependent Bim Modulation Downstream of the 4-1BB-TRAF1 Signaling Axis Is a Critical Mediator of CD8 T Cell Survival In Vivo J. Immunol., June 15, 2008; 180(12): 8093 - 8101. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mehrotra, A. Chhabra, U. Hegde, N. G. Chakraborty, and B. Mukherji Inhibition of c-Jun N-terminal kinase rescues influenza epitope-specific human cytolytic T lymphocytes from activation-induced cell death J. Leukoc. Biol., February 1, 2007; 81(2): 539 - 547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mehrotra, A. Chhabra, S. Chattopadhyay, D. I. Dorsky, N. G. Chakraborty, and B. Mukherji Rescuing Melanoma Epitope-Specific Cytolytic T Lymphocytes from Activation-Induced Cell Death, by SP600125, an Inhibitor of JNK: Implications in Cancer Immunotherapy J. Immunol., November 15, 2004; 173(10): 6017 - 6024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Snyder, T. Nakajima, P. J. Leibson, C. M. Weyand, and J. J. Goronzy Stimulatory Killer Ig-Like Receptors Modulate T Cell Activation through DAP12-Dependent and DAP12-Independent Mechanisms J. Immunol., September 15, 2004; 173(6): 3725 - 3731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Bertram, W. Dawicki, B. Sedgmen, J. L. Bramson, D. H. Lynch, and T. H. Watts A Switch in Costimulation from CD28 to 4-1BB during Primary versus Secondary CD8 T Cell Response to Influenza In Vivo J. Immunol., January 15, 2004; 172(2): 981 - 988. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Wilcox, K. Tamada, D. B. Flies, G. Zhu, A. I. Chapoval, B. R. Blazar, W. M. Kast, and L. Chen Ligation of CD137 receptor prevents and reverses established anergy of CD8+ cytolytic T lymphocytes in vivo Blood, January 1, 2004; 103(1): 177 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Prell, D. E. Evans, C. Thalhofer, T. Shi, C. Funatake, and A. D. Weinberg OX40-Mediated Memory T Cell Generation Is TNF Receptor-Associated Factor 2 Dependent J. Immunol., December 1, 2003; 171(11): 5997 - 6005. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Snyder, M. Lucas, E. Vivier, C. M. Weyand, and J. J. Goronzy Selective Activation of the c-Jun NH2-terminal Protein Kinase Signaling Pathway by Stimulatory KIR in the Absence of KARAP/DAP12 in CD4+ T Cells J. Exp. Med., February 17, 2003; 197(4): 437 - 449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Bansal-Pakala and M. Croft Defective T Cell Priming Associated with Aging Can Be Rescued by Signaling Through 4-1BB (CD137) J. Immunol., November 1, 2002; 169(9): 5005 - 5009. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Wen, J. Bukczynski, and T. H. Watts 4-1BB Ligand-Mediated Costimulation of Human T Cells Induces CD4 and CD8 T Cell Expansion, Cytokine Production, and the Development of Cytolytic Effector Function J. Immunol., May 15, 2002; 168(10): 4897 - 4906. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Wilcox, A. I. Chapoval, K. S. Gorski, M. Otsuji, T. Shin, D. B. Flies, K. Tamada, R. S. Mittler, H. Tsuchiya, D. M. Pardoll, et al. Expression of Functional CD137 Receptor by Dendritic Cells J. Immunol., May 1, 2002; 168(9): 4262 - 4267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Bertram, P. Lau, and T. H. Watts Temporal Segregation of 4-1BB Versus CD28-Mediated Costimulation: 4-1BB Ligand Influences T Cell Numbers Late in the Primary Response and Regulates the Size of the T Cell Memory Response Following Influenza Infection J. Immunol., April 15, 2002; 168(8): 3777 - 3785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Cannons, Y. Choi, and T. H. Watts Role of TNF Receptor-Associated Factor 2 and p38 Mitogen-Activated Protein Kinase Activation During 4-1BB-Dependent Immune Response J. Immunol., December 1, 2000; 165(11): 6193 - 6204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Arbour, D. Naniche, D. Homann, R. J. Davis, R. A. Flavell, and M. B.A. Oldstone c-Jun NH2-Terminal Kinase (JNK)1 and JNK2 Signaling Pathways Have Divergent Roles in CD8+ T Cell-mediated Antiviral Immunity J. Exp. Med., March 25, 2002; 195(7): 801 - 810. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
