Evidence for a primarily humoral rejection mechanism in concordant xenogeneic heart transplantation. A sequential immunohistological study in a hamster-to-rat model.

Heterotopic heart transplantations in an unmodified hamster-to-rat model were studied sequentially by immunohistochemical analysis. Monoclonal mouse anti-rat antibodies against B cells, T cells, macrophages and neutrophilic granulocytes (MRC OX-19, MRC OX-38, MRC OX-8, MRC OX-22, MRC OX-33, MRC OX-41 and MRC OX-42) were used in an indirect immunoperoxidase technique and monoclonal mouse anti-rat IgM and IgG were used for immunofluorescence. In grafts investigated after 6 h (N = 8) minimal infiltration of macrophages was demonstrated with MRC OX-41+ and MRC OX-42+ cells. No T- or B cells were seen. In a few cases, deposition of IgG and IgM was seen related to the endothelium of larger vessels. In grafts examined 24 h after transplantation (N = 10) the number of MRC OX-41+ and MRC OX-42+ cells had increased and in half of the cases IgM and IgG were located in relation to endothelial cells of larger vessels. In grafts investigated 48 h after transplantation (N = 8) the infiltration with MRC OX-41+ and MRC OX-42+ cells had further increased and a few scattered MRC OX-19+ and MRC OX-8+ cells appeared. At this time all but one heart had deposition of IgG and IgM in the vessel walls. Upon complete rejection (N = 8) diffuse infiltration of MRC OX-41+ and MRC OX-42+ cells was seen, but still only a few scattered T cells could be demonstrated. At this time IgG an IgM deposition appeared in all vessels and was also located in relation to the capillaries. These results further support our hypothesis that acute xenograft rejection in this animal model is primarily of the humoral type.