Detection of membrane-bound and soluble-form MHC class I antigen from rat pancreas/spleen grafts during ongoing rejection

Abstract

From the early stages of transplantation immunology, donor-specific unresponsiveness to the allogeneic heart graft has been known to be induced by combined transplantation with the donor-vascularized splenic graft.[1] This tolerance can be achieved without immunosuppressive drugs [1 and 2] or by use of a short course of such agents. [2. H. Suzuki, X.H. Li, M. Miyamoto et al.. Transplantation 64 (1997), p. 650. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (13)2, 3 and 4] This phenomenon is also observed in the transplantation combination of other lymphocyte-rich organs, such as liver [5] and lung, [3] supporting the hypothesis that donor cell migration from the lymphoid organs plays an important role in transplantation tolerance. [6] In an earlier report, we showed that donor-specific tolerance to the allogeneic pancreas graft could be induced in a pancreas/spleen transplantation (PST) model in a low responder combination of DA into PVG/c rat under a short course of cyclosporine (CsA), but that maintenance of this unresponsiveness was independent of the number of donor cells in the combined transplanted spleen.[4] We then tested a short course of immunosuppressants (CsA and/or rapamycin [RAPA]) on survival of the pancreas graft with the spleen in a high responder combination of DA into LEW rat. Although a significant prolongation of pancreas graft survival was observed, all of these grafts were finally rejected under this immunosuppressive protocol. To define whether donor “living” cells still remain in the host organs in the process of rejection, detection of membrane-bound MHC class I antigen, which is expressed in the intact donor cells, was tested using samples from animals with an ongoing rejection episode.