THE CELLULAR BASIS OF ALLOGRAFT REJECTION IN VIVO

Abstract

An adoptive transfer model was used to examine the subpopulations of lymphocytes required to effect 1st-set rejection of directly vascularized heart allografts. PVG [rat] heart grafts are not rejected in irradiated DA [rat] hosts for at least 50 days. The adoptive transfer of 5 .times. 107 syngeneic lymph node cells (LNC) restores rejection to 14.4 .+-. 2.4 days (mean .+-. SD). Subpopulations of LNC, were separated by an indirect panning technique using the mouse antirat monoclonal antibodies W3/13, MRC OX8, or W3/25 to deplete the unwanted subsets of cells. Each subpopulation was tested, in a number equivalent to the number present in 5 .times. 107 normal LNC, for its ability to cause the rejection of heart grafts. Whole T cells (W3/13+) on helper/inducer T cells (W3/25+) restored graft rejection to 16.4 .+-. 3.8 days and 16.0 .+-. 2.4 days, respectively. Neither cytotoxic/suppressor T cells (MRC OX8+) nor B cells (Ig+) restored rejection. Indirect immunoperoxidase stains of the grafts showed that although W3/25+ cells predominated in the rejected tissue, MRC OX8+ cells were also present even in grafts from rats restored with inocula that contained < 1% MRC OX8+ cells. Examination of lymphoid tissues suggested that the MRC OX8+ cells might be of host origin. By the time the grafts were rejected in irradiated hosts, significant thymic regeneration had occurred and there were large numbers of MRC OX8+ cells present in the thymus, as well as some in lymph nodes and spleen.