The profile of cytokine mRNA expression and immune cell infiltration in the rejection of allo- and xenogeneic skin transplantation

Kim, Jae Young; Ahn, Curie; Kim, Ki Won; Park, Joon Oh; Kim, Donghee; Lee, Eun Mi; Oh, Byung Hee; Lee, Jung Sang

Abstract

BACKGROUND
The immune response to xenogeneic organ transplants is stronger than that to allogeneic transplants and this extra strength results from the existence of preformed natural antibodies. However even in situation such as skin grafting, where antibody-mediated mechanisms are not thought to play a role, cell-mediated xenograft immunity is more potent than that to allograft. The mechanisms have not been well established yet. In the present study therefore we attempted to demonstrate the mechanism by the examination of the profiles of cytokine mRNA expression and immune cell infiltration in the Lewis rat-to-C57BL/6J mouse skin xenografts and the fully allogeneic BALB/c mouse-to-C57BL/6J mouse skin grafts.
METHODS
C57BL/6J mice were grafted with tail skins from Lewis rat and MHC class I/II different BALB/c mouse. The profiles of cytokine mRNA expression and infiltrated immune cells in both grafts harvested on days 3, 5, 7 and 9 after grafting were examined by quantitative RT-PCR and immunohistochemical analysis.
RESULTS
The mean survival time of xenogeneic skin grafts was 8.5+/-0.6 days, which was two days shorter than that of allogeneic skin grafts (10.3+/-0.5). The quantitative PCR analysis of intragraft cytokine expression revealed that the levels of IFN-gamma, IL-6 and IL-1beta in the xenografts were significantly up-regulated as compared to those in the allografts. The immunohistochemical analysis demonstrated that CD8+ T, CD11b+ and F4/80+ cells were more rapidly and severely infiltrated into the xenogeneic skin grafts as compared to those into the allogeneic grafts.
CONCLUSION
Overall results indicate that the cell-mediated immune responses to allo- and xenogeneic skin grafts may be exerted by T lymphocytes, neutrophils, NK cells and macrophages in a complicated manner and rapid rejection of xenogeneic skin grafts may be due to more rapid and severe infiltration of CD8+ T, CD11b+ and F4/80+ cells as compared to that of allogeneic grafts. In addition up-regulated proinflammatory cytokines such as IFN-gamma, IL-6 and IL-1beta in xenografts may be involved in the development and proliferation of these cells.