THE ROLE OF CYTOKINES DURING REJECTION OF FETAL PIG AND FETAL MOUSE PANCREAS GRAFTS IN NONOBESE DIABETIC MICE

The rejection of discordant foetal pig islet xenografts in nonimmunosu ppressed nonobese diabetic (NOD) mice is dominated by polymorphonuclea r cell infiltration whereas allografts are almost exclusively infiltra ted by mononuclear cells. To determine if this Variation is due to dif ferent proinflammatory factors generated al the graft site, we analyse d graft-site mRNA expression of various cytokines, and the eosinophil attractant chemokine, eotaxin, in a renal subcapsular islet transplant model using organ cultured foetal pig (xenograft) and foetal BALB/c ( allograft) pancreas in prediabetic NOD mice. Using semiquantitative RT -PCR on samples recovered at multiple lime points during the first 15 post-transplantation days from mice transplanted with either allogenei c or xenogeneic tissue, we found increased expression of IL-2, IL-4, T NF-beta and IL-10 mRNAs at the peak of the cellular infiltrate (on day 5) in both xenografts and allografts but, in contrast to the allograf ts, no enhanced transcription of IFN-gamma mRNA in the rejecting xenog rafts. When an allograft and a xenograft were placed at the opposite p ole of the same kidney the histological appearance of the rejecting al lograft site resembled the xenograft site with significant numbers of eosinophils in both, and enhanced expression of eotaxin and iNOS. Addi tionally, the xenograft response, unlike the allograft response, was m arked by an early increased expression of TNF-alpha and IL-S (day 3) a nd an almost complete absence of IFN-gamma expression. The results sug gest a distinct cell-mediated mechanism for rejection of foetal pancre as xenografts compared to the rejection of foetal pancreas allografts.