Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Biology, Cell Biology, Life Sciences & Biomedicine - Other Topics, 0601 Biochemistry and Cell Biology, 0606 Physiology, 1116 Medical Physiology, 3101 Biochemistry and cell biology, 3208 Medical physiology

Abstract:

Engagment of fas (CD95) on target cells by fas ligand (CD95l) bearing cytotoxic T lymphocytes (CTL) may be important for cell killing in allograft rejection. Tissues that co-express CD951 and MHC molecules can engage CD95 on allogeneic CTLs inducing apoptosis and promoting allograft tolerance. Here we have investigated, by immunohistochemistry with specific antibodies, expression of CD95 and CD95l in biopsies from 36 liver transplant recipients including: a) long term stable allografts b) mild rejection not requiring treatment c) severe acute rejection subsequently treated with high-dose corticosteroids; or d) established chronic rejection. Long term stable allografts and biopsies from patients with mild acute rejection showed minimal or negative staining for CD95 or CD951. Expression of CD95 was markedly increased in severe acute rejection on leukocytes, sinusoidal cells and vascular endothelium. CD951 was expressed strongly on the inflammatory cells and on sinusoidal cells. In chronic rejection, CD95 and CD951 expression persisted, particularly on sinusoidal cells and inflammatory cells. We conclude that 1) The intensity of CD95 expression on target cells in acute rejection may determine whether rejection is mild and self-limiting or more severe, requiring treatment with high-dose steroids or progressing to chronic rejection. 2) The strong expression of CD95 on target cells in association with CD951 expression in infiltrating leukocytes in severe rejection suggests that CD95-mediated cell death is an important mechanism of liver cell damage in rejection. 3) CD951 is not expressed in non-inflamed liver and is thus unlikely to be involved in the induction of tolerance.