Pig but not human interferon-γ initiates human cell-mediated rejection of pig tissue in vivo

Parvez Sultan, Allan G. Murray, Jennifer M. Mcniff, Marc I. Lorber, Philip W. Askenase, Alfred L.M. Bothwell, Jordan S. Pober

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Split-thickness pig skin was transplanted on severe combined immunodeficient mice so that pig dermal microvessels spontaneously inosculated with mouse microvessels and functioned to perfuse the grafts. Pig endothelial cells in the healed grafts constitutively expressed class I and class II major histocompatibility complex molecules. Major histocompatibility complex molecule expression could be further increased by intradermal injection of pig interferon-γ, (IFN-γ) but not human IFN-γ, or tumor necrosis factor. Grafts injected with pig IFN-γ also developed a sparse infiltrate of mouse neutrophils and eosinophils without evidence of injury. Introduction of human peripheral blood mononuclear cells into the animals by intraperitoneal inoculation resulted in sparse perivascular mononuclear cell infiltrates in the grafts confined to the pig dermis. Injection of pig skin grafts on mice that received human peripheral blood mononuclear cells with pig IFN-γ (but not human IFN-γ or heat-inactivated pig IFN-γ) induced human CD4+ and CD8+ T cells and macrophages to more extensively infiltrate the pig skin grafts and injure pig dermal microvessels. These findings suggest that human T cell-mediated rejection of xenotransplanted pig organs may be prevented if cellular sources of pig interferon (e.g., passenger lymphocytes) are eliminated from the graft.

Original languageEnglish (US)
Pages (from-to)8767-8772
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number16
DOIs
StatePublished - Aug 5 1997
Externally publishedYes

ASJC Scopus subject areas

  • General

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