Multiple pathways in the rejection of skin grafts

We have analyzed the ability of CD4+ and CD8+ T cells to cause rejection of skin grafts in an Ir gene high responder strain. (DA.RT1u x DA.RT1c)F1 B rats (thymectomized, lethally irradiated, reconstituted with fetal liver cells) were grafted with ear skin of the recombinant strain, DA.RT1rl. The only allogeneic difference was a single class I MHC antigen. The B rats, which do not reject these grafts due to the absence of T cells, were reconstituted at various time intervals after skin grafting with either unsorted lymph node cells (LNCs), CD4+, CD8+ or CD4+ and CD8+ T cells. Unsorted LNCs given any time after graft placement always caused rejection (MST = 15d). CD4+ cells alone never caused rejection (MST greater than 60d, n = 8). CD8+ cells alone caused rejection if given within 3 weeks of graft placement. Thereafter, CD8+ cells alone lost their ability to cause rejection (MST greater than 60d, n = 6). B rats with grafts in place more than 3 weeks, when CD8+ cells alone were ineffective, rejected their skin grafts when given both CD8+ and CD4+ cells. These data suggest that there may be two T cell pathways in skin graft rejection. The first requires only CD8+ cells and causes rejection of a recently placed graft. The second pathway requires both CD4+ and CD8+ cells to reject long-standing grafts in which donor antigen-presenting cells have been putatively depleted and, therefore, may be dependent on host antigen-presenting cells.