Characterization of Allograft Rejection in an Experimental Model of Small Intestinal Transplantation

被引：22

作者：

Hayashi M. ^{[1
]}

Martinez O.M. ^{[1
,3
]}

Krams S.M. ^{[1
]}

Burns W. ^{[2
]}

Esquivel C.O. ^{[1
]}

机构：

[1] Department of Surgery, Transplant Immunobiology Laboratory, Stanford Univ. School of Medicine, Stanford, CA

[2] Department of Pathology, California Pacific Medical Center, San Francisco, CA

[3] Stanford Univ. School of Medicine, MSLS, MC: 5492, Stanford

来源：

Journal of Gastrointestinal Surgery | 1998年 / 2卷 / 4期

关键词：

Tacrolimus; Allograft Rejection; Graft Rejection; Cytokine Gene Expression; Intestinal Transplantation;

D O I：

10.1016/S1091-255X(98)80071-1

中图分类号：

学科分类号：

摘要：

Graft rejection continues to be a major barrier to the success of clinical small intestinal transplantation. The objective of this study was to characterize histopathologic and immune parameters of allograft rejection in an experimental model of small intestinal transplantation. Heterotopic intestinal transplants were performed in allogeneic and isogeneic rat strain combinations. An additional group of allogeneic recipients was treated with tacrolimus (1 mgAg/day) for 7 days beginning on posttransplant day 1. Recipients of allografts and isografts were killed on days 1 to 7 following transplantation, and tacrolimus-treated allograft recipients were killed on days 4 and 7. Grafts and native intestines were examined for histopathology and cytokine gene expression. Very early rejection was observed on posttransplant day 3 and severe rejection was apparent by day 7. The key histopathologic features of acute graft rejection including apoptosis, crypt epithelial cell injury, and an inflammatory infiltrate were uniformly identifiable on day 4 and progressed in severity through day 7. Interleukin (IL)-2, IL-4, IL-5, IL-6, interferon-γ (IFN-γ), and tumor necrosis factor-α mRNA were readily detectable in allografts on days 1 to 7. However, only IFN-γ mRNA showed a significant early and sustained increase in allografts as compared to isografts and native intestine. Treatment of allograft recipients with tacrolimus abrogated the major histopathologic features of rejection and markedly inhibited IFN-γ gene expression. These results indicate that graft rejection in small intestinal transplantation is characterized by a local and specific immune response marked by IFN-γ production that results in crypt epithelial cell injury and apoptosis. Tacrolimus abrogates the histopathologic features of rejection in association with a marked inhibition of IFN-γ gene expression.

引用

页码：325 / 332

页数：7

共 23 条

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