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American Journal of Pathology, Vol 147, 834-844, Copyright © 1995 by American Society for Investigative Pathology

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A comparison of organ cultured fetal pancreas allo-, iso-, and xenografts (pig) in non-immunosuppressed non-obese diabetic mice

TE Mandel, J Kovarik and M Koulmanda
Transplantation Unit, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.

The response of non-immunosuppressed non-obese diabetic/Lt mice to an isograft (H-2g7), major histocompatibility complex-mismatched allografts (CBA, H-2K; BALB/c, H-2d), and xenograft of fetal pig pancreas was assessed by light microscopy. In non-obese diabetic mice, isografts were rapidly invaded by lymphoid cells, and the graft pathology was similar to that in the host pancreas. In prediabetic mice the graft site was invaded by small mononuclear cells (CD4 and CD8+ve T cells) and macrophages, and in diabetic mice specific beta-cell destruction was found. The allografts were invaded and destroyed within 10 to 14 days by mononuclear cells that included many blast cells. In the allograft sites the infiltrating cells soon disappeared, and within 3 weeks only a scar remained. The xenografts, in contrast, were invaded by macrophages and eosinophils with some neutrophils and mast cells and multinucleated giant cells. Xenograft destruction also occurred over 8 to 10 days, but the site remained large and swollen with a central necrotic zone and massive fibrosis forming a large granuloma, and the infiltrate persisted for many weeks. Thus, there are marked differences in the host response to a challenge with tissue that is prone to cell- specific autoimmune disease, to a graft of immunogenic allogeneic tissue, and to a transplant of discordant xenogeneic islets. Because of the differences in the host response to these grafts different immunosuppressive strategies may be needed to cope with their destruction.

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