Acute cell-mediated rejection in orthotopic pig-to-mouse corneal xenotransplantation

Xenotransplantation. 2009 Mar-Apr;16(2):74-82. doi: 10.1111/j.1399-3089.2009.00514.x.

Abstract

Background: To investigate the role of T cells and natural killer (NK) cells in mediating corneal xenograft rejection in a pig-to-mouse model.

Methods: Pig corneas were orthotopically transplanted into BALB/c, C57BL/6, nude, severe combined immunodeficiency (SCID), and NOD/SCID/gammac(null) (NOG) mice. Graft survival was clinically assessed by slit-lamp biomicroscopy and median survival times (MST) were calculated. The rejected grafts were histologically evaluated using antibodies against CD4, CD8, NK1.1, and F4/80.

Results: The pig corneal xenografts were acutely rejected by BALB/c and C57BL/6 mice (MST 9.0 days), while nude, SCID and NOG mice rejected pig corneas in a more delayed fashion (MST 16.0, 16.4, and 16.9 days, respectively). The majority of infiltrating cells found in rejected grafts in C57BL/6 mice were macrophages and CD4(+) T cells, while CD8(+) T cells and NK cells were rarely found. The grafts in nude mice had markedly decreased inflammatory infiltration with small numbers of macrophages and CD4(+) T cells. Infiltration was even more modest in grafts in SCID and NOG mice.

Conclusions: T cells play an important role in acute rejection of pig corneal xenografts in mice, although acute rejection is not solely the result of T-cell-mediated immunity. NK cells are less likely to be involved in the rejection process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cornea / pathology
  • Corneal Transplantation / immunology*
  • Graft Rejection / immunology*
  • Graft Survival / immunology
  • Humans
  • Killer Cells, Natural / immunology*
  • Mice
  • Mice, Inbred BALB C / immunology
  • Mice, Inbred C57BL / immunology
  • Mice, Inbred NOD / immunology
  • Mice, Nude / immunology
  • Mice, SCID / immunology
  • Sus scrofa / immunology
  • T-Lymphocytes / immunology*
  • Transplantation, Heterologous / immunology*