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Accelerated acute rejection of the intestinal graft in CD28-deficient mice.

Journal article
Authors G. Dindelegan
Mihai Oltean
Göran Kurlberg
Nils Y Lycke
Ola Nilsson
Michael Olausson
Published in Transplantation proceedings
Volume 37
Issue 1
Pages 82-6
ISSN 0041-1345
Publication year 2007
Published at Institute of Biomedicine, Department of Pathology
Institute of Biomedicine, Department of Microbiology and Immunology
Institute of Clinical Sciences
Pages 82-6
Language en
Links dx.doi.org/10.1016/j.transproceed.2...
Keywords Acute Disease, Animals, Antigens, CD28, genetics, Gene Deletion, Graft Rejection, genetics, immunology, pathology, Intestinal Mucosa, pathology, transplantation, Intestine, Small, parasitology, transplantation, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Microcirculation, immunology, pathology, Transplantation, Homologous, immunology, pathology
Subject categories Medical and Health Sciences

Abstract

OBJECTIVE: Multiple in vivo studies have shown that the pace and severity of graft rejection is little or not at all changed by deleting CD28 molecules in the recipient. These findings contrast with the effects of monoclonal antibody therapy aimed the same costimulatory target. The objective of the present study was to evaluate how the acute rejection process is affected in CD28-deficient mice using a fully allogeneic, highly immunologically reactive transplant model. METHODS: Heterotopic vascularized small bowel transplants were performed in 24 recipient mice divided into 4 groups: 2 wild-type and 2 knockout groups. Each group consisted of 5 to 7 animals in which BalbC mice were used as intestinal donors to either wild-type C57BL6 or C57BL6 background CD28-deficient recipient mice. Selected endpoints were 3 and 6 postoperative days (POD). Intestinal rejection was evaluated by mucosal laser Doppler flowmetry (expressed in perfusion units) and histology (expressed in rejection grades). RESULTS: Acute rejection occurred in both wild-type and CD28-deficient groups. At POD 3, no significant difference was noted between groups in terms of mucosal perfusion and histology. At POD 6, significant differences in graft mucosal perfusion and histology revealed a more aggressive rejection in the CD28-deficient group compared to the wild-type group. CONCLUSIONS: The present study showed that the severity of intestinal graft rejection responses was amplified by deleting CD28 molecules. Together with data from other studies, these results suggest a different pattern of distribution and/or activation of CD28/B7 receptors in various organs.

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