CELLULAR REJECTION OF FETAL PANCREAS GRAFTS - DIFFERENCES BETWEEN ALLOGRAFT AND XENOGRAFT REJECTION

Hyperacute rejection (HAR) is the major immunologic problem with vascu larized xenografts between discordant donor/recipient combinations but does not occur in neovascularized grafts of organ-cultured fetal pig pancreas in either mice or cynomolgus monkeys. However, a form of cell -mediated acute rejection with quite different histopathologic feature s does occur with kinetics that are similar to acute cellular rejectio n of fetal pancreas allografts in non-immunosuppressed MHC-mismatched mice. Xenograft rejection is dominated by nonlymphoid cells, mostly eo sinophils, that appear some days after transplantation. In contrast, i n mouse allografts, mononuclear cells are the dominant population thro ughout the rejection process. The rejected allograft site rapidly reso lves to form a mature non-infiltrated scar whereas the infiltrate in t he xenograft site remains for weeks and forms a large granuloma before its eventual resolution. There are also differences in the intra-graf t cytokine profile in the graft site between allo- and xenografts duri ng acute rejection with an early predominance of IL-5 and TNF-alpha an d an absence of INF-gamma in the xenografts. Immunosuppression with a depleting anti-CD4 mAb shows that xenograft rejection is more dependen t on CD4+ve T cells but xenografts are more difficult to maintain with conventional immunosuppression that is often effective for allografts . Limited studies in primates have shown that the histopathology of fe tal pig pancreas rejection is similar to that seen in mice but occurs at a faster tempo. Thus, although HAR may not be a problem in rejectio n of neovascularised xenografts, a vigorous form of cellular rejection is present that may require different immunosuppression than is usual ly used for the control of allograft rejection.