Cellular rejection in discordant xenografts when hyperacute rejection is prevented: analysis using adoptive and passive transfer.

TitleCellular rejection in discordant xenografts when hyperacute rejection is prevented: analysis using adoptive and passive transfer.
Publication TypeJournal Article
Year of Publication1994
AuthorsFryer JP, Leventhal JR, Dalmasso AP, Chen S, Simone PA, Jessurun J, Sun LH, Reinsmoen NL, Matas AJ
JournalTranspl Immunol
Date Published1994 Jun
KeywordsAcute Disease, Animals, Complement Inactivator Proteins, Elapid Venoms, Graft Enhancement, Immunologic, Graft Rejection, Guinea Pigs, Heart Transplantation, Immunization, Passive, Immunoglobulin G, Immunoglobulin M, Immunohistochemistry, Immunotherapy, Adoptive, Rats, Rats, Inbred Lew, Transplantation, Heterologous

Hyperacute rejection of discordant xenografts occurs rapidly, precluding cellular infiltration. Thus the role of cellular rejection in discordant xenografts is debated. Using adoptive transfer of sensitized splenocytes and passive transfer of sensitized serum, we evaluated the influence of cellular and humoral elements on cellular infiltration and rejection in the guinea-pig-to-rat discordant xenograft model. Guinea-pig hearts were transplanted into Lewis rats. Pretransplant, rats underwent splenectomy and plasma exchange and were started on daily cobra venom factor injections. Xenografts rejected faster after adoptive (1, 2, 2 and 2 days) or passive (1, 1, 2 and 2 days) transfer than controls (4, 4, 4 and 4 days; p < 0.05). Macrophages and neutrophils were predominant in early prerejection specimens. Over time, cellular infiltrates were dominated by mononuclear cells. Natural killer cells were present in all groups, as were interleukin 2 receptor positive cells. Our data suggest that either sensitized serum or sensitized cells are capable of initiating an accelerated rejection characterized by cellular infiltration. Despite subtle differences, the population of infiltrating cells was similar in each group. Thus, although rejection may be initiated by either cellular or humoral influences, the ultimate result is the same. We have, therefore, established a small animal model to study cellular rejection in discordant xenografts. This model will help evaluate the role of cell subsets and xenoantibodies in xenograft rejection and will help determine the precise relationship between the two when hyperacute rejection is prevented.

Alternate JournalTranspl Immunol
PubMed ID7953323
Grant ListDK13083 / DK / NIDDK NIH HHS / United States
Related Faculty: 
Jose Jessurun, M.D.

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