This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by El-Sawy, T. Articles by Fairchild, R. Search for Related Content PubMed PubMed Citation Articles by El-Sawy, T. Articles by Fairchild, R.

(American Journal of Pathology. 2004;165:147-157.)
© 2004 American Society for Investigative Pathology

Early T Cell Response to Allografts Occuring Prior to Alloantigen Priming Up-Regulates Innate-Mediated Inflammation and Graft Necrosis

Tarek El-Sawy^*, Masayoshi Miura^* and Robert Fairchild^*

From the Department of Immunology,^* Lerner Research Institute, The Cleveland Clinic Foundation; and The Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio

The early inflammatory response within organ allografts is initiated by ischemia/reperfusion (I/R) and promotes subsequent alloantigen-primed T cell recruitment into and rejection of the graft. Polymorphonuclear leukocyte (PMN)-mediated tissue damage is a primary component of the early inflammation in allograft rejection. We sought to compare and elucidate the mechanism of early PMN infiltration into cardiac isografts and allografts. Despite identical production of PMN attractant chemokines, PMN infiltration following reperfusion into syngeneic and allogeneic grafts was not equivalent. PMN infiltration into isografts peaked at 9 to 12 hours post-transplant and quickly resolved. In contrast, PMN infiltration into allografts continued to elevated levels, peaking at 24 hours post-reperfusion. This amplified PMN infiltration into allografts did not resolve until 72 hours post-reperfusion and was accompanied by marked parenchymal necrosis. This early innate inflammatory response was regulated by IFN--producing CD8⁺ T cells present in the recipient before detectable alloantigen T cell priming. Co-culture with CD62L^low CD8⁺ T cells, but not CD62L^high CD8⁺ or CD62L^low CD4⁺ T cells, harvested from naïve animals induced allogeneic endothelial cells to express IFN--dependent chemokines. These data demonstrate CD8⁺ T cell-mediated attack on the vascular endothelium of allografts within hours following organ reperfusion that amplifies innate immune-mediated intra-graft inflammation and necrosis.

This article has been cited by other articles:

				N. Kesteman, G. Vansanten, B. Pajak, S. M. Goyert, and M. Moser Injection of lipopolysaccharide induces the migration of splenic neutrophils to the T cell area of the white pulp: role of CD14 and CXC chemokines J. Leukoc. Biol., March 1, 2008; 83(3): 640 - 647. [Abstract] [Full Text] [PDF]

				A. Valujskikh and X. C. Li Frontiers in Nephrology: T Cell Memory as a Barrier to Transplant Tolerance J. Am. Soc. Nephrol., August 1, 2007; 18(8): 2252 - 2261. [Full Text] [PDF]

				N. Shimoda, N. Fukazawa, K. Nonomura, and R. L. Fairchild Cathepsin G Is Required for Sustained Inflammation and Tissue Injury after Reperfusion of Ischemic Kidneys Am. J. Pathol., March 1, 2007; 170(3): 930 - 940. [Abstract] [Full Text] [PDF]

				M. A. Brehm, J. Mangada, T. G. Markees, T. Pearson, K. A. Daniels, T. B. Thornley, R. M. Welsh, A. A. Rossini, and D. L. Greiner Rapid quantification of naive alloreactive T cells by TNF-{alpha} production and correlation with allograft rejection in mice Blood, January 15, 2007; 109(2): 819 - 826. [Abstract] [Full Text] [PDF]

				R. Maile, C. M. Barnes, A. I. Nielsen, A. A. Meyer, J. A. Frelinger, and B. A. Cairns Lymphopenia-Induced Homeostatic Proliferation of CD8+ T Cells Is a Mechanism for Effective Allogeneic Skin Graft Rejection following Burn Injury. J. Immunol., June 1, 2006; 176(11): 6717 - 6726. [Abstract] [Full Text] [PDF]

				D. G. Healy, R. W. G. Watson, C. O'Keane, J. J. Egan, J. F. McCarthy, J. Hurley, J. Fitzpatrick, and A. E. Wood Neutrophil transendothelial migration potential predicts rejection severity in human cardiac transplantation. Eur. J. Cardiothorac. Surg., May 1, 2006; 29(5): 760 - 766. [Abstract] [Full Text] [PDF]

				D. Chen, N. Zhang, S. Fu, B. Schroppel, Q. Guo, A. Garin, S. A. Lira, and J. S. Bromberg CD4+CD25+ Regulatory T-Cells Inhibit the Islet Innate Immune Response and Promote Islet Engraftment. Diabetes, April 1, 2006; 55(4): 1011 - 1021. [Abstract] [Full Text] [PDF]

				V. T. Enoh, C. Y. Lin, T. K. Varma, and E. R. Sherwood Differential effect of imipenem treatment on injury caused by cecal ligation and puncture in wild-type and NK cell-deficient {beta}2-microgloblin knockout mice Am J Physiol Gastrointest Liver Physiol, February 1, 2006; 290(2): G277 - G284. [Abstract] [Full Text] [PDF]

				T. El-Sawy, J. A. Belperio, R. M. Strieter, D. G. Remick, and R. L. Fairchild Inhibition of Polymorphonuclear Leukocyte-Mediated Graft Damage Synergizes With Short-Term Costimulatory Blockade to Prevent Cardiac Allograft Rejection Circulation, July 19, 2005; 112(3): 320 - 331. [Abstract] [Full Text] [PDF]

				T. Engeman, A. V. Gorbachev, D. D. Kish, and R. L. Fairchild The intensity of neutrophil infiltration controls the number of antigen-primed CD8 T cells recruited into cutaneous antigen challenge sites J. Leukoc. Biol., November 1, 2004; 76(5): 941 - 949. [Abstract] [Full Text] [PDF]