| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
The Carlos and Marguerite Mason Transplantation Research Center, Renal Division, Department of Medicine, Emory University and Veterans Affairs Medical Center, Atlanta, GA 30033; and
Pathology and Laboratory Medicine, Veterans Affairs Medical Center and State University of New York, Buffalo, NY 14215
We examined whether IL-2 regulates alloimmune responses by studying allograft survival in wild-type (IL-2+/+) and IL-2 gene-knockout (IL-2-/-) mice. The acute rejection of vascularized, cardiac allografts and the generation of allospecific CTLs were not impaired in the absence of IL-2. In contrast, blocking the B7-CD28 T cell costimulation pathway with CTLA4Ig induced long-term allograft survival (>100 days) in IL-2+/+ recipients but failed to do so in IL-2-/- mice or in wild-type mice that had been treated with IL-2-neutralizing Ab around the time of transplantation. Allografts rejected by IL-2-/- recipients exhibited extensive mononuclear cell infiltrates despite CTLA4Ig administration. In vivo allostimulation in the absence of IL-2 led to exaggerated T lymphocyte proliferation and impaired apoptosis of activated T cells in untreated and CTLA4Ig-treated mice. These findings indicate that endogenous IL-2 is required for the induction of long-term allograft survival, and that IL-2 regulates alloimmune responses by preparing activated T lymphocytes for alloantigen-induced apoptosis.
This article has been cited by other articles:
|
|
 |
|
  D. Tchorsh-Yutsis, G. Hecht, A. Aronovich, E. Shezen, Y. Klionsky, C. Rosen, R. Bitcover, S. Eventov-Friedman, H. Katchman, S. Cohen, et al. Pig Embryonic Pancreatic Tissue as a Source for Transplantation in Diabetes: Transient Treatment With Anti-LFA1, Anti-CD48, and FTY720 Enables Long-Term Graft Maintenance in Mice With Only Mild Ongoing Immunosuppression Diabetes, July 1, 2009; 58(7): 1585 - 1594. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Mangada, T. Pearson, M. A. Brehm, L. S. Wicker, L. B. Peterson, L. D. Shultz, D. V. Serreze, A. A. Rossini, and D. L. Greiner Idd Loci Synergize to Prolong Islet Allograft Survival Induced by Costimulation Blockade in NOD Mice Diabetes, January 1, 2009; 58(1): 165 - 173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Jiang, F. Pan, L. M. Erickson, M.-S. Jang, T. Sanui, Y. Kunisaki, T. Sasazuki, M. Kobayashi, and Y. Fukui Deletion of DOCK2, a regulator of the actin cytoskeleton in lymphocytes, suppresses cardiac allograft rejection J. Exp. Med., October 17, 2005; 202(8): 1121 - 1130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Sawitzki, C. I. Kingsley, V. Oliveira, M. Karim, M. Herber, and K. J. Wood IFN-{gamma} production by alloantigen-reactive regulatory T cells is important for their regulatory function in vivo J. Exp. Med., June 20, 2005; 201(12): 1925 - 1935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Pearson, P. Weiser, T. G. Markees, D. V. Serreze, L. S. Wicker, L. B. Peterson, A.-M. Cumisky, L. D. Shultz, J. P. Mordes, A. A. Rossini, et al. Islet Allograft Survival Induced by Costimulation Blockade in NOD Mice Is Controlled by Allelic Variants of Idd3 Diabetes, August 1, 2004; 53(8): 1972 - 1978. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. B. Strom, L. J. Field, and M. Ruediger Allogeneic Stem Cell-Derived "Repair Unit" Therapy and the Barriers to Clinical Deployment J. Am. Soc. Nephrol., May 1, 2004; 15(5): 1133 - 1139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. H. Nelson IL-2, Regulatory T Cells, and Tolerance J. Immunol., April 1, 2004; 172(7): 3983 - 3988. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. G. Lakkis Transplantation tolerance: a journey from ignorance to memory Nephrol. Dial. Transplant., October 1, 2003; 18(10): 1979 - 1982. [Full Text] [PDF]
|
|
|
|
|
|
A. Bose, Y. Inoue, K. E. Kokko, and F. G. Lakkis Cutting Edge: Perforin Down-Regulates CD4 and CD8 T Cell-Mediated Immune Responses to a Transplanted Organ J. Immunol., February 15, 2003; 170(4): 1611 - 1614. [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]
|
|
|
|
|
|
M. Afrouzian, V. Ramassar, J. Urmson, L.-F. Zhu, and P. F. Halloran Transcription Factor IRF-1 in Kidney Transplants Mediates Resistance to Graft Necrosis during Rejection J. Am. Soc. Nephrol., May 1, 2002; 13(5): 1199 - 1209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rabinovitch, W. L. Suarez-Pinzon, A.M. J. Shapiro, R. V. Rajotte, and R. Power Combination Therapy With Sirolimus and Interleukin-2 Prevents Spontaneous and Recurrent Autoimmune Diabetes in NOD Mice Diabetes, March 1, 2002; 51(3): 638 - 645. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sanchez-Fueyo, M. Weber, C. Domenig, T. B. Strom, and X. X. Zheng Tracking the Immunoregulatory Mechanisms Active During Allograft Tolerance J. Immunol., March 1, 2002; 168(5): 2274 - 2281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Jones, J. Ha, M. A. Williams, A. B. Adams, M. M. Durham, P. A. Rees, S. R. Cowan, T. C. Pearson, and C. P. Larsen The Role of the IL-2 Pathway in Costimulation Blockade-Resistant Rejection of Allografts J. Immunol., February 1, 2002; 168(3): 1123 - 1130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Pimenta-Araujo, L. Mascarell, M. Huesca, A. Cumano, and A. Bandeira Embryonic Thymic Epithelium Naturally Devoid of APCs Is Acutely Rejected in the Absence of Indirect Recognition J. Immunol., November 1, 2001; 167(9): 5034 - 5041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yan, S. Shastry, C. Richards, C. Wang, D. G. Bowen, A. F. Sharland, D. M. Painter, G. W. McCaughan, and G. A. Bishop Posttransplant Administration of Donor Leukocytes Induces Long-Term Acceptance of Kidney or Liver Transplants by an Activation-Associated Immune Mechanism J. Immunol., April 15, 2001; 166(8): 5258 - 5264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. K. Bishop, S. C. Wood, E. J. Eichwald, and C. G. Orosz Immunobiology of Allograft Rejection in the Absence of IFN-{{gamma}}: CD8+ Effector Cells Develop Independently of CD4+ Cells and CD40-CD40 Ligand Interactions J. Immunol., March 1, 2001; 166(5): 3248 - 3255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Rothstein, M. F. A. Livak, K. Kishimoto, C. Ariyan, H.-Y. Qian, S. Fecteau, M. Sho, S. Deng, X. X. Zheng, M. H. Sayegh, et al. Targeting Signal 1 Through CD45RB Synergizes with CD40 Ligand Blockade and Promotes Long Term Engraftment and Tolerance in Stringent Transplant Models J. Immunol., January 1, 2001; 166(1): 322 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Dai, B. T. Konieczny, and F. G. Lakkis The Dual Role of IL-2 in the Generation and Maintenance of CD8+ Memory T Cells J. Immunol., September 15, 2000; 165(6): 3031 - 3036. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Gorczynski, Z. Chen, D. A. Clark, J. Hu, G. Yu, X. Li, W. Tsang, and S. Hadidi Regulation of Gene Expression of Murine MD-1 Regulates Subsequent T Cell Activation and Cytokine Production J. Immunol., August 15, 2000; 165(4): 1925 - 1932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Dai, A. Arakelov, M. Wagener, B. T. Konieczny, and F. G. Lakkis The Role of the Common Cytokine Receptor {gamma}-Chain in Regulating IL-2-Dependent, Activation-Induced CD8+ T Cell Death J. Immunol., September 15, 1999; 163(6): 3131 - 3137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. C. Li, Y. Li, I. Dodge, A. D. Wells, X. X. Zheng, L. A. Turka, and T. B. Strom Induction of Allograft Tolerance in the Absence of Fas-Mediated Apoptosis J. Immunol., September 1, 1999; 163(5): 2500 - 2507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bushell, M. Niimi, P. J. Morris, and K. J. Wood Evidence for Immune Regulation in the Induction of Transplantation Tolerance: A Conditional but Limited Role for IL-4 J. Immunol., February 1, 1999; 162(3): 1359 - 1366. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
