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CUTTING EDGE |
Departments of
*
Medicine and
Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110
CD28 provides an important costimulatory signal in T cell activation that regulates multiple cellular processes including proliferation and survival. Several signal transduction pathways are activated by CD28; however, the precise biochemical mechanism by which CD28 regulates T cell function remains controversial. Retroviral gene transfer into primary T cells from TCR-transgenic, CD28-deficient mice was used to determine the specific sequences within CD28 that determine function. Discrete regions of the cytoplasmic domain of CD28 were identified that differentially regulate T cell proliferation and induction of the anti-apoptotic protein Bcl-XL. Mutation of C-terminal proline residues abrogated the proliferative and cytokine regulatory features of CD28 costimulation while preserving Bcl-XL induction. Conversely, mutation of residues important in phosphatidylinositol 3-kinase activation partially inhibited proliferation but prevented induction of Bcl-XL. Thus the ability of CD28 to regulate proliferation and induction of Bcl-XL map to distinct motifs, suggesting independent signaling cascades modulate these biologic effects.
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H.-W. Lee, S.-J. Park, B. K. Choi, H. H. Kim, K.-O. Nam, and B. S. Kwon 4-1BB Promotes the Survival of CD8+ T Lymphocytes by Increasing Expression of Bcl-xL and Bfl-1 J. Immunol., November 1, 2002; 169(9): 4882 - 4888. [Abstract] [Full Text] [PDF]
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R. G. Jones, A. R. Elford, M. J. Parsons, L. Wu, C. M. Krawczyk, W.-C. Yeh, R. Hakem, R. Rottapel, J. R. Woodgett, and P. S. Ohashi CD28-dependent Activation of Protein Kinase B/Akt Blocks Fas-mediated Apoptosis by Preventing Death-inducing Signaling Complex Assembly J. Exp. Med., August 5, 2002; 196(3): 335 - 348. [Abstract] [Full Text] [PDF]
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Q. Ye, B. Press, S. Kissler, X.-F. Yang, L. Lu, C. H. Bassing, B. P. Sleckman, M. Jansson, V. Panoutsakopoulou, L. A. Trimble, et al. T Cell Costimulation through CD28 Depends on Induction of the Bcl-x{gamma} Isoform: Analysis of Bcl-x{gamma}-deficient Mice J. Exp. Med., July 1, 2002; 196(1): 87 - 95. [Abstract] [Full Text] [PDF]
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J. A. Cook, A. August, and A. J. Henderson Recruitment of Phosphatidylinositol 3-Kinase to CD28 Inhibits HIV Transcription by a Tat-Dependent Mechanism J. Immunol., July 1, 2002; 169(1): 254 - 260. [Abstract] [Full Text] [PDF]
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P. Ghosh, M. A. Buchholz, S. Yano, D. Taub, and D. L. Longo Effect of rapamycin on the cyclosporin A-resistant CD28-mediated costimulatory pathway Blood, May 29, 2002; 99(12): 4517 - 4524. [Abstract] [Full Text] [PDF]
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N. D. L. Savage, S. L. Kimzey, S. K. Bromley, K. G. Johnson, M. L. Dustin, and J. M. Green Polar Redistribution of the Sialoglycoprotein CD43: Implications for T Cell Function J. Immunol., April 15, 2002; 168(8): 3740 - 3746. [Abstract] [Full Text] [PDF]
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