| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Center for Neurologic Diseases, and
Laboratory of Immunogenetics and Transplantation, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115
Injection of Ag into the thymus of adult animals induces specific systemic tolerance. The mechanisms of acquired thymic tolerance include anergy and the deletion of Ag-specific T cells. Here, we report that anergy to nominal Ag induced via acquired thymic tolerance requires CTL-associated Ag 4 (CTLA4) engagement. The role of CTLA4 in the induction and maintenance of tolerance was then investigated in the murine experimental autoimmune encephalomyelitis model. CTLA4 blockade abrogated the induction but not the maintenance phase of acquired thymic tolerance induced by intrathymic injection of myelin Ags. In addition, CTLA4 blockade had a restricted window of action after priming with Ag, which is consistent with the expression patterns of CTLA4 in vivo. We conclude that: 1) the induction of acquired thymic tolerance requires signaling through CTLA4 and 2) CTLA4 does not appear to be required for the maintenance of acquired thymic tolerance. This is the first report documenting the role of a CTLA4 negative signaling pathway in the induction of tolerance in an autoimmune disease model.
This article has been cited by other articles:
|
|
 |
|
  R. M. Gorczynski, Z. Chen, W. He, I. Khatri, Y. Sun, K. Yu, and I. Boudakov Expression of a CD200 Transgene Is Necessary for Induction but Not Maintenance of Tolerance to Cardiac and Skin Allografts J. Immunol., August 1, 2009; 183(3): 1560 - 1568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Song, Z. Guan, I. E. Gienapp, T. Shawler, J. Benson, and C. C. Whitacre The Thymus Plays a Role in Oral Tolerance in Experimental Autoimmune Encephalomyelitis J. Immunol., August 1, 2006; 177(3): 1500 - 1509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Homann, W. Dummer, T. Wolfe, E. Rodrigo, A. N. Theofilopoulos, M. B. A. Oldstone, and M. G. von Herrath Lack of Intrinsic CTLA-4 Expression Has Minimal Effect on Regulation of Antiviral T-Cell Immunity J. Virol., January 1, 2006; 80(1): 270 - 280. [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]
|
|
|
|
 |
|
 A. D. Salama, T. Chitnis, J. Imitola, M. J. I. Ansari, H. Akiba, F. Tushima, M. Azuma, H. Yagita, M. H. Sayegh, and S. J. Khoury Critical Role of the Programmed Death-1 (PD-1) Pathway in Regulation of Experimental Autoimmune Encephalomyelitis J. Exp. Med., July 7, 2003; 198(1): 71 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sho, A. Yamada, N. Najafian, A. D. Salama, H. Harada, S. E. Sandner, A. Sanchez-Fueyo, X. X. Zheng, T. B. Strom, and M. H. Sayegh Physiological Mechanisms of Regulating Alloimmunity: Cytokines, CTLA-4, CD25+ Cells, and the Alloreactive T Cell Clone Size J. Immunol., October 1, 2002; 169(7): 3744 - 3751. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kinjo, N. Takasu, I. Komiya, T. Tomoyose, M. Takara, T. Kouki, Y. Shimajiri, K. Yabiku, and H. Yoshimura Remission of Graves' Hyperthyroidism and A/G Polymorphism at Position 49 in Exon 1 of Cytotoxic T Lymphocyte-Associated Molecule-4 Gene J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2593 - 2596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-F. Bai, J. Liu, K. F. May Jr, Y. Guo, P. Zheng, and Y. Liu B7-CTLA4 interaction promotes cognate destruction of tumor cells by cytotoxic T lymphocytes in vivo Blood, April 15, 2002; 99(8): 2880 - 2889. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Yamada, A. D. Salama, and M. H. Sayegh The Role of Novel T Cell Costimulatory Pathways in Autoimmunity and Transplantation J. Am. Soc. Nephrol., February 1, 2002; 13(2): 559 - 575. [Full Text] [PDF]
|
|
|
|
|
|
K. A. Frauwirth, M.-L. Alegre, and C. B. Thompson CTLA-4 Is Not Required for Induction of CD8+ T Cell Anergy In Vivo J. Immunol., November 1, 2001; 167(9): 4936 - 4941. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Yamada, K. Kishimoto, V. M. Dong, M. Sho, A. D. Salama, N. G. Anosova, G. Benichou, D. A. Mandelbrot, A. H. Sharpe, L. A. Turka, et al. CD28-independent Costimulation of T Cells in Alloimmune Responses J. Immunol., July 1, 2001; 167(1): 140 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Griffin, D. K. Hong, P. O. Holman, K.-M. Lee, M. J. Whitters, S. M. O'Herrin, F. Fallarino, M. Collins, D. M. Segal, T. F. Gajewski, et al. Blockade of T Cell Activation Using a Surface-Linked Single-Chain Antibody to CTLA-4 (CD152) J. Immunol., May 1, 2000; 164(9): 4433 - 4442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Frauwirth, M.-L. Alegre, and C. B. Thompson Induction of T Cell Anergy in the Absence of CTLA-4/B7 Interaction J. Immunol., March 15, 2000; 164(6): 2987 - 2993. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. B. Ratts, L. R. Arredondo, P. Bittner, P. J. Perrin, A. E. Lovett-Racke, and M. K. Racke The role of CTLA-4 in tolerance induction and T cell differentiation in experimental autoimmune encephalomyelitis: i.p. antigen administration Int. Immunol., December 1, 1999; 11(12): 1881 - 1888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. B. Ratts, L. R. Arredondo, P. Bittner, P. J. Perrin, A. E. Lovett-Racke, and M. K. Racke The role of CTLA-4 in tolerance induction and Ttigen administration cell differentiation in experimental autoimmune encephalomyelitis: i.v. antigen administration Int. Immunol., December 1, 1999; 11(12): 1889 - 1896. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Luhder, C. Chambers, J. P. Allison, C. Benoist, and D. Mathis Pinpointing when T cell costimulatory receptor CTLA-4 must be engaged to dampen diabetogenic T cells PNAS, October 24, 2000; 97(22): 12204 - 12209. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
