| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
CUTTING EDGE |
Departments of
*
Surgery and
Medicine, Yale Medical School, New Haven, CT 06520; Departments of
Medicine and
Surgery, University of Massachusetts Medical School, Worcester, MA 01655; and Departments of
¶ Pathology and
|| Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA 02115
Knockout and blocking studies have shown a critical role for CTLA-4 in peripheral tolerance, however, it is unknown whether augmenting CTLA-4 expression actually promotes tolerance. Here we demonstrate a specific and requisite role for CTLA-4 and its up-regulation in tolerance through anti-CD45RB. First, long-term murine islet allograft survival induced by anti-CD45RB is prevented by CTLA4-Ig, which interferes with B7:CTLA-4 interactions. Second, anti-CD45RB is ineffective in recipients lacking CTLA-4, B7-1, and B7-2. In contrast, CTLA4-Ig, which targets B7 on allogeneic cells, promotes long-term engraftment in these mice. Moreover, anti-CD45RB was effective in B7-deficient controls expressing CTLA-4. Finally, in wild-type mice, CTLA-4 expression returned to baseline 17 days after receiving anti-CD45RB, and was refractory to further increase. Transplantation and anti-CD45RB therapy at this time could neither augment CTLA-4 nor prolong engraftment. These data demonstrate a specific role for CTLA-4 in anti-CD45RB-mediated tolerance and indicate that CTLA-4 up-regulation can directly promote allograft survival.
This article has been cited by other articles:
|
|
 |
|
  A. L. Tang, J. R. Teijaro, M. N. Njau, S. S. Chandran, A. Azimzadeh, S. G. Nadler, D. M. Rothstein, and D. L. Farber CTLA4 Expression Is an Indicator and Regulator of Steady-State CD4+FoxP3+ T Cell Homeostasis J. Immunol., August 1, 2008; 181(3): 1806 - 1813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Y. Jen, M. Campo, H. He, S. S. Makani, G. Velasco, D. M. Rothstein, D. L. Perkins, and P. W. Finn CD45RB Ligation Inhibits Allergic Pulmonary Inflammation by Inducing CTLA4 Transcription J. Immunol., September 15, 2007; 179(6): 4212 - 4218. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-C. Chang, Y.-T. Chang, Y.-W. Tien, P.-C. Liang, I-S. Jan, S.-C. Wei, and J.-M. Wong T-Cell Regulatory Gene CTLA-4 Polymorphism/Haplotype Association with Autoimmune Pancreatitis Clin. Chem., September 1, 2007; 53(9): 1700 - 1705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Deng, D. J. Moore, X. Huang, M.-M. Lian, M. Mohiuddin, E. Velededeoglu, M. K. Lee IV, S. Sonawane, J. Kim, J. Wang, et al. Cutting Edge: Transplant Tolerance Induced by Anti-CD45RB Requires B Lymphocytes J. Immunol., May 15, 2007; 178(10): 6028 - 6032. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Narang and R. I. Mahato Biological and biomaterial approaches for improved islet transplantation. Pharmacol. Rev., June 1, 2006; 58(2): 194 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Lim, R. M. Sutherland, Y. Zhan, G. Deliyannis, L. E. Brown, and A. M. Lew Targeting CD45RB alters T cell migration and delays viral clearance Int. Immunol., February 1, 2006; 18(2): 291 - 300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. H. Tan, J. B. Yates, S.-A. Xue, C. Chan, W. J. Jordan, J. E. Harper, M. P. Watson, R. Dong, M. A. Ritter, R. I. Lechler, et al. Creation of tolerogenic human dendritic cells via intracellular CTLA4: a novel strategy with potential in clinical immunosuppression Blood, November 1, 2005; 106(9): 2936 - 2943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sho, K. Kishimoto, H. Harada, M. Livak, A. Sanchez-Fueyo, A. Yamada, X. X. Zheng, T. B. Strom, G. P. Basadonna, M. H. Sayegh, et al. Requirements for induction and maintenance of peripheral tolerance in stringent allograft models PNAS, September 13, 2005; 102(37): 13230 - 13235. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Attia, G. Q. Phan, A. V. Maker, M. R. Robinson, M. M. Quezado, J. C. Yang, R. M. Sherry, S. L. Topalian, U. S. Kammula, R. E. Royal, et al. Autoimmunity Correlates With Tumor Regression in Patients With Metastatic Melanoma Treated With Anti-Cytotoxic T-Lymphocyte Antigen-4 J. Clin. Oncol., September 1, 2005; 23(25): 6043 - 6053. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. V. Aruna, M. Sela, and E. Mozes Suppression of myasthenogenic responses of a T cell line by a dual altered peptide ligand by induction of CD4+CD25+ regulatory cells PNAS, July 19, 2005; 102(29): 10285 - 10290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Czuczman, A. Thall, T. E. Witzig, J. M. Vose, A. Younes, C. Emmanouilides, T. P. Miller, J. O. Moore, J. P. Leonard, L. I. Gordon, et al. Phase I/II Study of Galiximab, an Anti-CD80 Antibody, for Relapsed or Refractory Follicular Lymphoma J. Clin. Oncol., July 1, 2005; 23(19): 4390 - 4398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-X. Chen, H. He, and R. M. Gorczynski Synthetic peptides from the N-terminal regions of CD200 and CD200R1 modulate immunosuppressive and anti-inflammatory effects of CD200-CD200R1 interaction Int. Immunol., March 1, 2005; 17(3): 289 - 296. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
