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 Chai, J.-G. Articles by Lechler, R. Search for Related Content PubMed PubMed Citation Articles by Chai, J.-G. Articles by Lechler, R.

CD152 Ligation by CD80 on T Cells Is Required for the Induction of Unresponsiveness by Costimulation-Deficient Antigen Presentation¹

Jian-Guo Chai^2,*, Silvia Vendetti^2,*, Eunice Amofah^*, Julian Dyson and Robert Lechler^3,*

^* Department of Immunology, Imperial College School of Medicine, and Transplantation Biology Group, Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom

Two apparently contradictory observations have been made concerning peripheral T cell tolerance; costimulation-deficient Ag presentation leads to unresponsiveness, and CTLA4 (CD152) ligation is required for unresponsiveness to be induced. This issue was addressed using a CD80^- CD86^low B cell line to present Ag to DO.11.10 naive CD4⁺ T cells. Proliferation was substantially enhanced by anti-CD80 or anti-CD152, but was inhibited by anti-CD86. Furthermore, anti-CD80 partially, and anti-CD152 totally protected cloned DO.11.10 T cells from the induction of unresponsiveness following culture with peptide and Chinese hamster ovary H2-A^d+ CD80^- CD86^- cells. Fab of anti-CD80 caused similar enhancement, and coimmobilized anti-CD80 failed to costimulate the anti-CD3 response of purified T cells, indicating that direct signaling by anti-CD80 was not responsible for these effects. The possibility that anti-CD80 liberated CD28 molecules that were sequestered by the T cell-expressed CD80, enabling them to coaggregate with TCR:CD3 complexes was excluded by finding that anti-CD80 and anti-CD152 individually caused maximal enhancement, rather than having additive effects. These data suggest that T cell-expressed CD80 has a regulatory function and plays a key role in the induction of unresponsiveness due to costimulation-deficient Ag presentation by the ligation of CD152 on neighboring, or even the same, T cell.

This article has been cited by other articles:

				Y. Li, L. Ma, D. Yin, J. Shen, and A. S. Chong Long-Term Control of Alloreactive B Cell Responses by the Suppression of T Cell Help J. Immunol., May 1, 2008; 180(9): 6077 - 6084. [Abstract] [Full Text] [PDF]

				C. Q. Nie, N. J. Bernard, L. Schofield, and D. S. Hansen CD4+ CD25+ Regulatory T Cells Suppress CD4+ T-Cell Function and Inhibit the Development of Plasmodium berghei-Specific TH1 Responses Involved in Cerebral Malaria Pathogenesis Infect. Immun., May 1, 2007; 75(5): 2275 - 2282. [Abstract] [Full Text] [PDF]

				A. P. Treschow, J. Backlund, R. Holmdahl, and S. Issazadeh-Navikas Intrinsic Tolerance in Autologous Collagen-Induced Arthritis Is Generated by CD152-Dependent CD4+ Suppressor Cells J. Immunol., June 1, 2005; 174(11): 6742 - 6750. [Abstract] [Full Text] [PDF]

				L. A. Stephens, A. N. Barclay, and D. Mason Phenotypic characterization of regulatory CD4+CD25+ T cells in rats Int. Immunol., February 1, 2004; 16(2): 365 - 375. [Abstract] [Full Text] [PDF]

				C. Vasu, S. R. Gorla, B. S. Prabhakar, and M. J. Holterman Targeted engagement of CTLA-4 prevents autoimmune thyroiditis Int. Immunol., May 1, 2003; 15(5): 641 - 654. [Abstract] [Full Text] [PDF]

				C. Vasu, A. Wang, S. R. Gorla, S. Kaithamana, B. S. Prabhakar, and M. J. Holterman CD80 and CD86 C domains play an important role in receptor binding and co-stimulatory properties Int. Immunol., February 1, 2003; 15(2): 167 - 175. [Abstract] [Full Text] [PDF]

				S. Vendetti, A. Riccomi, A. Sacchi, L. Gatta, C. Pioli, and M. T. De Magistris Cyclic Adenosine 5'-Monophosphate and Calcium Induce CD152 (CTLA-4) Up-Regulation in Resting CD4+ T Lymphocytes J. Immunol., December 1, 2002; 169(11): 6231 - 6235. [Abstract] [Full Text] [PDF]

				M. Gonzalez, S. A. Quezada, B. R. Blazar, A. Panoskaltsis-Mortari, A. Y. Rudensky, and R. J. Noelle The Balance Between Donor T Cell Anergy and Suppression Versus Lethal Graft-Versus-Host Disease Is Determined by Host Conditioning J. Immunol., November 15, 2002; 169(10): 5581 - 5589. [Abstract] [Full Text] [PDF]

				E. A. Tivol and J. Gorski Re-establishing Peripheral Tolerance in the Absence of CTLA-4: Complementation by Wild-Type T Cells Points to an Indirect Role for CTLA-4 J. Immunol., August 15, 2002; 169(4): 1852 - 1858. [Abstract] [Full Text] [PDF]

				J. L. LaBelle, C. A. Hanke, B. R. Blazar, and R. L. Truitt Negative effect of CTLA-4 on induction of T-cell immunity in vivo to B7-1+, but not B7-2+, murine myelogenous leukemia Blood, March 15, 2002; 99(6): 2146 - 2153. [Abstract] [Full Text] [PDF]

				T. L. Vanasek, A. Khoruts, T. Zell, and D. L. Mueller Antagonistic Roles for CTLA-4 and the Mammalian Target of Rapamycin in the Regulation of Clonal Anergy: Enhanced Cell Cycle Progression Promotes Recall Antigen Responsiveness J. Immunol., November 15, 2001; 167(10): 5636 - 5644. [Abstract] [Full Text] [PDF]

				C. Noel, S. Florquin, M. Goldman, and M. Y. Braun Chronic exposure to superantigen induces regulatory CD4+ T cells with IL-10-mediated suppressive activity Int. Immunol., April 1, 2001; 13(4): 431 - 439. [Abstract] [Full Text] [PDF]