HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yu, X.-Z. Articles by Anasetti, C. Search for Related Content PubMed PubMed Citation Articles by Yu, X.-Z. Articles by Anasetti, C.

CD28 Signal Enhances Apoptosis of CD8 T Cells After Strong TCR Ligation ¹

Xue-Zhong Yu^2,*, Paul J. Martin^*, and Claudio Anasetti^*,

^* Human Immunogenetics Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and Department of Medicine, University of Washington, Seattle, WA 98195

High avidity ligation of the TCR induces negative selection in the thymus and can also induce apoptosis of peripheral T cells. Costimulation through CD28 enhances T cell activation and facilitates negative selection in the thymus, but the role of CD28 in peripheral T cell deletional tolerance has not been investigated. We used 2C CD28 wild-type and 2C CD28-deficient strains to assess the effects of CD28 and TCR avidity on peripheral T cell expansion and apoptosis. We compared the activation, division, expansion, and apoptosis of CD28^+/+ and CD28^-/- 2C cells in response to self-Ag (K^b), alloantigens with intermediate (K^bm3), high (L^d), or very high (L^d + QL9 peptide) avidity. With intermediate avidity alloantigen, the CD28 signal enhanced T cell activation and expansion. However, when T cells encountered high avidity alloantigen, the CD28 signal reduced T cell expansion and increased apoptosis. These results indicate that the CD28 signal can down-regulate peripheral T cell responses by increasing apoptosis when TCR ligation exceeds a critical threshold.

This article has been cited by other articles:

				S. Mostbock, S. Vidal, J. Schlom, and H. Sabzevari Enhanced Levels of Costimulation Lead to Reduced Effector/Memory CD8+ T Cell Functionality J. Immunol., September 15, 2007; 179(6): 3524 - 3534. [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]

				X.-Z. Yu, M. H. Albert, and C. Anasetti Alloantigen Affinity and CD4 Help Determine Severity of Graft-versus-Host Disease Mediated by CD8 Donor T Cells J. Immunol., March 15, 2006; 176(6): 3383 - 3390. [Abstract] [Full Text] [PDF]

				S. Yang, J. W. Hodge, D. W. Grosenbach, and J. Schlom Vaccines with Enhanced Costimulation Maintain High Avidity Memory CTL J. Immunol., September 15, 2005; 175(6): 3715 - 3723. [Abstract] [Full Text] [PDF]

				S. Mukherjee, A. Ahmed, and D. Nandi CTLA4-CD80/CD86 interactions on primary mouse CD4+ T cells integrate signal-strength information to modulate activation with Concanavalin A J. Leukoc. Biol., July 1, 2005; 78(1): 144 - 157. [Abstract] [Full Text] [PDF]

				J.-X. Gao, X. Chang, X. Zheng, J. Wen, L. Yin, P. Du, P. Zheng, and Y. Liu A new role for CD28 in the survival of autoreactive T cells in the periphery after chronic exposure to autoantigen Int. Immunol., October 1, 2004; 16(10): 1403 - 1409. [Abstract] [Full Text] [PDF]

				M.-C. Michallet, F. Saltel, M. Flacher, J.-P. Revillard, and L. Genestier Cathepsin-Dependent Apoptosis Triggered by Supraoptimal Activation of T Lymphocytes: A Possible Mechanism of High Dose Tolerance J. Immunol., May 1, 2004; 172(9): 5405 - 5414. [Abstract] [Full Text] [PDF]