| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada
CD28 provides important signals that lower the threshold of T cell activation, augment the production of IL-2, and promote T cell survival. The recent identification of a second family of costimulatory molecules within the TNFR family has reshaped the "two-signal" model of T cell activation. In this study the role of p75 as a T cell costimulatory molecule in controlling cell fate during TCR/CD28-mediated stimulation was examined. We found that p75-deficient T cells possess a profound defect in IL-2 production in response to TCR/CD28-mediated stimulation. Examination of key signaling intermediates revealed that TCR proximal events such as global tyrosine phosphorylation and ZAP70 phosphorylation, as well as downstream MAPK cascades are unperturbed in p75-deficient T cells. In contrast, p75 is nonredundantly coupled to sustained AKT activity and NF-
B activation in response to TCR/CD28-mediated stimulation. Moreover, p75-deficient T cells possess a defect in survival during the early phase of T cell activation that is correlated with a striking defect in Bcl-xL expression. These data indicate discrete effects of p75 on the intracellular signaling milieu during T cell activation, and reveal the synergistic requirement of TCR, CD28, and p75 toward optimal IL-2 induction and T cell survival. We propose that p75 acts as one of the earliest of the identified costimulatory members of the TNFR family, and is functionally linked to CD28 for initiating and determining T cell fate during activation.
This article has been cited by other articles:
|
|
 |
|
  E. Y. Kim, S.-J. Teh, J. Yang, M. T. Chow, and H.-S. Teh TNFR2-Deficient Memory CD8 T Cells Provide Superior Protection against Tumor Cell Growth J. Immunol., November 15, 2009; 183(10): 6051 - 6057. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nie, M. Cornberg, and L. K. Selin Resistance to Vaccinia Virus Is Less Dependent on TNF under Conditions of Heterologous Immunity J. Immunol., November 15, 2009; 183(10): 6554 - 6560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. McKarns and R. H. Schwartz Biphasic Regulation of Il2 Transcription in CD4+ T Cells: Roles for TNF-{alpha} Receptor Signaling and Chromatin Structure J. Immunol., July 15, 2008; 181(2): 1272 - 1281. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Baumel, A. Lechner, T. Hehlgans, and D. N. Mannel Enhanced susceptibility to Con A-induced liver injury in mice transgenic for the intracellular isoform of human TNF receptor type 2 J. Leukoc. Biol., July 1, 2008; 84(1): 162 - 169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Chatzidakis, G. Fousteri, D. Tsoukatou, G. Kollias, and C. Mamalaki An Essential Role for TNF in Modulating Thresholds for Survival, Activation, and Tolerance of CD8+ T Cells J. Immunol., June 1, 2007; 178(11): 6735 - 6745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhao, M. Mohaupt, J. Jiang, S. Liu, B. Li, and Z. Qin Tumor Necrosis Factor Receptor 2-Mediated Tumor Suppression Is Nitric Oxide Dependent and Involves Angiostasis Cancer Res., May 1, 2007; 67(9): 4443 - 4450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Munroe and G. A. Bishop A Costimulatory Function for T Cell CD40 J. Immunol., January 15, 2007; 178(2): 671 - 682. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Goldstein, S. Ben-Horin, A. Koltakov, H. Chermoshnuk, V. Polevoy, Y. Berkun, N. Amariglio, and I. Bank {alpha}1beta1 Integrin+ and Regulatory Foxp3+ T Cells Constitute Two Functionally Distinct Human CD4+ T Cell Subsets Oppositely Modulated by TNF{alpha} Blockade J. Immunol., January 1, 2007; 178(1): 201 - 210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Valencia, G. Stephens, R. Goldbach-Mansky, M. Wilson, E. M. Shevach, and P. E. Lipsky TNF downmodulates the function of human CD4+CD25hi T-regulatory cells Blood, July 1, 2006; 108(1): 253 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-G. Zhang, C. Liu, K. Su, S. Yu, L. Zhang, S. Zhang, J. Wang, X. Cao, W. Grizzle, and R. P. Kimberly A Membrane Form of TNF-{alpha} Presented by Exosomes Delays T Cell Activation-Induced Cell Death. J. Immunol., June 15, 2006; 176(12): 7385 - 7393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. B. Thornley, M. A. Brehm, T. G. Markees, L. D. Shultz, J. P. Mordes, R. M. Welsh, A. A. Rossini, and D. L. Greiner TLR Agonists Abrogate Costimulation Blockade-Induced Prolongation of Skin Allografts J. Immunol., February 1, 2006; 176(3): 1561 - 1570. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Y. Kim, J. J. Priatel, S.-J. Teh, and H.-S. Teh TNF Receptor Type 2 (p75) Functions as a Costimulator for Antigen-Driven T Cell Responses In Vivo J. Immunol., January 15, 2006; 176(2): 1026 - 1035. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
