Dendritic cells/chimerism/alleviation of chronic allograft rejection.

Chronic rejection (CR) is the major obstacle of long-term successful organ transplantation. Using a recently developed rat model of CR, we found that heart allografts susceptible to development of CR showed an early (< 10 days) dramatic disappearance of donor MHC class II+ cells, including ED2+ tissue macrophages, and an influx of recipient ED1+ macrophages intermixed with small numbers of recipient ED2+ and OX62+ cells. In contrast, donor MHC class II+ cells persisted in allografts resistant to CR with a small influx of recipient macrophages. MHC class II+ cells function as potent modulators of the immune system and may mediate both stimulatory and tolerogenic immune reactions after transplantation. Persistence of donor MHC class II+ antigen-presenting cells (APC) in CR-free graft acceptance suggests that transplantation tolerance is an active immune response requiring antigen presentation to the recipient immune system in the proper context by dendritic cells and other APC.