| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Section of Nephrology, Department of Internal Medicine, and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520;
Emory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322;
Pathology and Laboratory Medicine, Veterans Affairs Medical Center and State University of New York, Buffalo, NY 14215; and
Laboratory of Molecular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115
Transplanted organs fail due to either acute or chronic rejection. The prevailing view is that the nature or magnitude of the recipient’s immune response to donor Ags determines the type of rejection. In variance with this view, we show in this study that the status of the graft itself plays a dominant role in defining the type of rejection even in the face of an established alloimmune response. Using adoptive transfer mouse models in which the graft is exposed to a constant number of effector lymphocytes, we found that newly transplanted heart allografts are rejected acutely, while healed-in allografts undergo chronic rejection. Acute rejection of healed-in allografts was largely recapitulated by subjecting the grafts to ischemia-reperfusion injury similar to that present in newly transplanted organs. Ischemia-Reperfusion injury altered the outcome of rejection by enhancing the accumulation of effector T cells within the graft. The accumulation of effector T cells in the graft was dependent on the presence of both ischemia-reperfusion injury (inflammation) and alloantigens. These findings demonstrate that the graft plays a dominant role in shaping the outcome of rejection by controlling the trafficking of effector T cells.
This article has been cited by other articles:
|
|
 |
|
  D. A. Rao, K. J. Tracey, and J. S. Pober IL-1{alpha} and IL-1beta Are Endogenous Mediators Linking Cell Injury to the Adaptive Alloimmune Response J. Immunol., November 15, 2007; 179(10): 6536 - 6546. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. F. LaRosa, A. H. Rahman, and L. A. Turka The Innate Immune System in Allograft Rejection and Tolerance J. Immunol., June 15, 2007; 178(12): 7503 - 7509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Tellides and J. S. Pober Interferon-{gamma} Axis in Graft Arteriosclerosis Circ. Res., March 16, 2007; 100(5): 622 - 632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Chakraverty, D. Cote, J. Buchli, P. Cotter, R. Hsu, G. Zhao, T. Sachs, C. M. Pitsillides, R. Bronson, T. Means, et al. An inflammatory checkpoint regulates recruitment of graft-versus-host reactive T cells to peripheral tissues J. Exp. Med., August 7, 2006; 203(8): 2021 - 2031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Wildhirt, C. Schulze, N. Conrad, R. Bauernschmitt, R. Lange, and W. von Scheidt Persistently increased systemic, but not cardiac-specific, adhesion molecule expression and coronary endothelial dysfunction in human cardiac allografts J. Thorac. Cardiovasc. Surg., October 1, 2005; 130(4): 1175 - 1175. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
