A new XXXX model of islet xenograft rejection: graft destruction is dependent on a major histocompatibility-specific interaction between T-cells and macrophages.

@entity32 @entity14380 @entity19 @entity61 @entity630
A new @entity19 model of porcine @entity14380 ( @entity14380 ) xenograft rejection, avoiding interference of unspecific @entity32 , was introduced and used to investigate rejection mechanisms. Athymic (nu/nu) @entity19 were transplanted with syngeneic, allogeneic, or xenogeneic islets under the kidney capsule. After the original transplantation, immune cells in porcine @entity14380 xenografts undergoing rejection in native immunocompetent @entity19 were transferred to the peritoneal cavity of the athymic @entity19 . At defined time points after transfer, the primary grafts were evaluated by immunohistochemistry and real-time quantitative RT-PCR to estimate cytokine and chemokine mRNA expression. Transfer of immunocompetent cells enabled athymic (nu/nu) @entity19 to reject a previously tolerated @entity14380 xenograft only when donor and recipient were matched for major histocompatibility complex (MHC). In contrast, allogeneic and syngeneic islets were not rejected. The @entity14380 xenograft rejection was mediated by transferred T-cells. The main effector cells, macrophages, were shown to be part of a specific immune response. By day 4 after transplantation, there was an upreglation of both @entity630 - and @entity61 -associated cytokine transcripts. The transferred T-cells were xenospecific and required MHC compatibility to induce rejection. Interaction between the TCR of transferred T-cells and MHC on host endothelial cells and/or macrophages seems necessary for inducing @entity14380 xenograft rejection.
