Inverse relationship between liver γδT cells and Foxp3+CD25+CD4+ Tregs contributes to liver allograft tolerance and rejection (141.44)

Abstract

Abstract Our previous studies have demonstrated that Foxp3+CD25+CD4+ regulatory T (Treg) cells play an important role in inducing liver transplant tolerance. It is unknown whether γdT cells are involved in liver tolerance and how they interact with other types of cells. In this study, we examined the involvement of γdT cells in liver transplant tolerance by using an orthotopic liver transplantation model in which liver allografts are accepted spontaneously across the MHC barrier. Controls received either anti-CTLA4 mAb or anti-CD25 mAb pre- or peri-operatively, which induced acute liver allograft rejection. The majority of γdT cells were located in the liver and were CD4 and CD8 negative, did not express TCRαβ and NK receptors. In contrast to Foxp3+CD4+CD25+ Treg, γdT cells were decreased in the spontaneously tolerant liver allografts throughout the time courses from day 1 to day 100 posttransplantation and increased in the rejected liver grafts at day 5 posttransplantation. The CD4 and CD8 marker expression on γdT cells were increased in the tolerated livers post transplantation (10-20%). We speculate that the decreased number of γdT cells in the tolerated liver allografts may be due to the suppressive effect of Foxp3+CD4+CD25+ Treg. Therefore, γδ T cells, expressed in opposite frequency to Foxp3+CD4+CD25+ Treg, are involved in the processes of liver transplant tolerance.