Role of the spleen in cell-mediated cardiac allograft rejection.

Abstract

A quantitative adoptive transfer assay was used to investigate the role of the spleen in cell-mediated rejection of directly vascularized heart grafts. In this assay, the cell-mediated rejection response can be examined directly by testing the capacity of inocula of T cells to effect rejection of DA heart grafts in PVG rats whose own lymphocytes have been destroyed by whole body irradiation. The capacity of a variety of inocula, including lymph node cells (LNCs), spleen cells, and T cells from lymph node and spleen, to restore rejection were compared in groups of splenectomized and nonsplenectomized hosts. In both groups all inocula restored rejection toward normal. Only in experiments testing inocula equivalent to a small fraction of the naive peripheral lymphocyte pool was rejection delayed in the splenectomized hosts, and this was only a delay of a few days. These results showed that in the absence of the spleen, the primary rejection responses can be generated. In addition, it was demonstrated that the normal spleen contains only a small fraction of the T cell pool with the capacity to effect rejection. Memory T cells were also shown to mediate rejection in splenectomized hosts. It is concluded that with strongly incompatible grafts, splenectomy has only a trivial immunosuppressive effect; it removes neither a sigificant proportion of the alloreactive T cell pool nor the essential site for activation of proliferation of these cells.