Xenograft rejection of porcine islet-like cell clusters in normal, interferon-gamma, and interferon-gamma receptor deficient mice

Transplantation. 1997 May 27;63(10):1446-52. doi: 10.1097/00007890-199705270-00014.

Abstract

Background: The aim of the present study was to evaluate the role of the T-cell cytokine interferon (IFN)-gamma in mediating macrophage activation in xenograft rejection.

Methods: For this purpose, fetal porcine islet-like cell cluster (ICC) transplants were placed under the renal capsule of normal mice and mice with a homozygous targeted disruption of the IFN-gamma or the IFN-gamma receptor gene. Some of the mice were continuously infused with cyclosporine (CsA, 12.4 mg/kg body weight/day) or CsA vehicle by subcutaneously implanted osmotic pumps. Histological evaluation of the xenografts was performed 6 or 12 days after transplantation.

Results: All animals, irrespective of recipient group, readily rejected the ICC xenograft, although the rejection process was slightly delayed in mice deficient in IFN-gamma. Analysis of the infiltrating cells within the xenograft in knockout mice revealed a pattern similar to that found in control animals. Six days after transplantation, there was an abundant infiltration of macrophages (Mac-1, F4/80, and major histocompatibility complex II markers) in the ICC grafts. Quite in contrast, there was only a low to moderate number of T cells (CD3 marker) present in the ICC grafts. Treatment with CsA had no effect on the rejection process. In grafts removed from mice with a disruption of the IFN-gamma gene, occasional surviving endocrine cells, and in some cases also a few intact ICC, were found within the otherwise obliterated xenograft. Few or no surviving endocrine cells were found in the grafts obtained from the other groups of mice.

Conclusions: Thus, the present study demonstrates that macrophage activation, and subsequent destruction of an ICC xenograft, can operate in the absence of IFN-gamma in the pig-to-mouse model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclosporine / blood
  • Fluorescent Antibody Technique
  • Graft Rejection / metabolism
  • Immunohistochemistry
  • Immunosuppressive Agents / blood
  • Interferon-gamma / deficiency
  • Interferon-gamma / physiology*
  • Islets of Langerhans Transplantation / immunology*
  • Islets of Langerhans Transplantation / pathology
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Interferon / deficiency
  • Swine
  • Transplantation, Heterologous / immunology*
  • Transplantation, Heterologous / pathology

Substances

  • Immunosuppressive Agents
  • Receptors, Interferon
  • interferon gamma receptor
  • Interferon-gamma
  • Cyclosporine