Antigen presenting cells (APCs) play a central role in the activation of T-cells and the initiation the cellular immunologic response and, therefore, play a critical role in transplantation immunology. APCs are bone marrow derived cells which are present within all solid organs and are subsequently carried into allograft recipients. It is felt by some that donor APCs, which express MHC Class II antigens on their surface, are required for rejection. By replacing donor APCs with recipient-type APCs, we have shown that rejection still occurs, most likely through the indirect pathway of antigen presentation. However it is possible, although unlikely, that the rejection is a result of the presence of Class 11 antigens on graft endothelial cells. Although donor APCs do not appear to play an important role in rejection, they are felt to play a role in tolerance induction. To address these two questions, this study will use chimeric heart (i.e. hearts with parenchyma and APCs of differing genotype) transplantation to: (1) rule out the possibility that graft endothelium has sufficient APC function to trigger rejection using MHC Class II knockout mice, and (2) determine if APCs or other bone marrow-derived elements are required for tolerance induction. If APCs are found to play an important role in tolerance induction, clinical protocols could be developed to manipulate transplanted APCs to induce tolerance.
| Krasinskas, A M; Eiref, S D; McLean, A D et al. (2000) Replacement of graft-resident donor-type antigen presenting cells alters the tempo and pathogenesis of murine cardiac allograft rejection. Transplantation 70:514-21 |
