THE MAIN INFILTRATING CELL IN XENOGRAFT REJECTION IS A CD4(-LYMPHOCYTE() MACROPHAGE AND NOT A T)

Porcine fetal islet-like cell clusters (ICC) or isolated rat islets we re implanted under the kidney capsule of normoglycemic rats. The anima ls were sacrificed 1, 3, 6, 12, or 24 days after transplantation, and a detailed morphological and phenotypic characterization of the differ ent cellular subtypes infiltrating the xenograft was performed and com pared with the rejection of allogeneic islets. In xenograft rejection a progressive infiltration of large, polygonal, macrophage-like cells, which with time became the dominating cellular subtype, occurred. The se cells expressed the CD4 antigen and the macrophage-specific ED1 ant igen. From day 6 and onward, a majority of the macrophage-like cells a lso expressed the CD8 antigen and the macrophage-specific differentiat ion antigen ED2. T lymphocytes, defined by their TCR alpha/beta or CD2 expression, were found in low numbers and mainly in the periphery of the graft. At the later stages of xenorejection a substantial number o f eosinophilic granulocytes were also found. The allograft rejection, on the contrary, was characterized by a progressive infiltration of T lymphocytes, which with time became the dominating cellular subtype. N o clear immunoglobulin or complement deposition was seen in the transp lants before day 12, when IgG deposition was found in central necrotic areas of the xenograft. Previous experiments in rodents have underlin ed the crucial importance of CD4 positive cells in the xenograft rejec tion process. However, in none of these studies it was conclusively de monstrated that the CD4-expressing cells were T lymphocytes. The prese nce of CD4-expressing macrophages heavily infiltrating the porcine xen ograft seen in our study may thus be in agreement with previous studie s in which the anti-CD4 reactive cells were erroneously designated T l ymphocytes, Interestingly, the findings in xenograft rejection in the present study have striking similarities with the defense mechanisms a ctive against infections by large parasites such as helminths.