gammadeltaT cells are involved in liver transplant tolerance.

The role of nonconventional T cells in innate and adaptive immunity is just emerging; gammadeltaT cells play important roles in anti-tumor and anti-infectious diseases. The involvement of gammadeltaT cells in immunologic responses to hematopoietic cell transplantation remains controversial; divergent results have been reported depending on the murine strains and model systems. Whether gammadeltaT cells are involved in solid organ transplantation is understudied. We have characterized the gammadeltaT cells in mouse livers and spleens to evaluate their contributions to liver transplant tolerance posttransplantation using a murine allogeneic liver transplant model which induces spontaneous T regulatory cell (Treg)-dependent tolerance. Our studies revealed that gammadeltaT cells comprised about 20% of the population of liver nonparenchymal cells (NPCs). In naïve C3H mice they were CD4, CD8, and NK1.1 negative. The percentage of gammadeltaT cells decreased in spontaneously tolerated liver grafts posttransplantation from 20% in naïve C3H livers to <10% in allografts throughout the time course. In contrast, they increased in liver grafts with rejection induced by anti-CTLA4 plus anti-CD25 mAb administration. CD4 and CD8 expression on gammadeltaT cells dramatically increased in the tolerated but not rejected livers posttransplantation to >20% of CD4(+) and 30% of CD8(+). Our results suggested that gammadeltaT cells are involved in allogeneic immune responses. Whether gammadeltaT cells function as the causal or the effector cells in allograft tolerance rejection warrants further investigation.