EVIDENCE FOR A PRIMARILY HUMORAL REJECTION MECHANISM IN CONCORDANT XENOGENEIC HEART-TRANSPLANTATION - A SEQUENTIAL IMMUNOHISTOLOGICAL STUDYIN A HAMSTER-TO-RAT MODEL

Heterotopic heart transplantations in an unmodified hamster-to-rat mod el were studied sequentially by immunohistochemical analysis. Monoclon al 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 immunope roxidase technique and monoclonal mouse anti-rat IgM and IgG were used for immunofluorescence. In grafts investigated after 6 h (N=8) minima l infiltration of macrophages was demonstrated with MRC OX-41(+) and M RC OX-42(+) cells. No T- or B cells were seen. In a few cases, deposit ion of IgG and IgM was seen related to the endothelium of larger vesse ls. 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 IgC were located in relation to endothelial cells of lar ger vessels. In grafts investigated 48 h after transplantation (N=8) t he infiltration with MRC OX-41(+) and MRC OX-42(+) cells had further i ncreased and a few scattered MRC OX-19(+) and MRC OX-8(+) cells appear ed. At this time all but one heart had deposition of IgG and IgM in th e 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 sca ttered T cells could be demonstrated. At this time IgG an IgM depositi on appeared in all vessels and was also located in relation to the cap illaries. These results further support our hypothesis that acute xeno graft rejection in this animal model is primarily of the humoral type.