IFN-γ Control of an Effector/Target Combination for Skin Allograft Rejection: Macrophage/Skin Components in Normal Mice or T Cell/Endothelial Cells in IFN-γ-Deficient Mice

J Interferon Cytokine Res. 2020 Apr;40(4):207-217. doi: 10.1089/jir.2019.0129. Epub 2020 Feb 18.

Abstract

Organ, skin, or cell allografts are acutely rejected from normal mice, whereas vascularized organ allografts, but not allografted Meth A cells, are rejected from interferon-γ (IFN-γ)-deficient mice. Here we explored effector/target combinations for i.p. allografted Meth A (cytotoxic T lymphocyte [CTL]-resistant) or RLmale1 (CTL-susceptible) cells into or for BALB/c skin (skin components: CTL resistant) onto normal or IFN-γ-deficient C57BL/6 mice. After allografting, normal mice showed more infiltration but only a little thrombosis/hemorrhage. Monocyte/macrophage MHC receptor (MMR)+ macrophages (on days 5-10) and T cell receptor (TCR)+ CTLs (on days 7-9) were cytotoxic against Meth A cells or skin components and RLmale1 cells, respectively, and the allografts were rejected. After allografting into IFN-γ-deficient mice, MMR- macrophages and highly activated TCR+ CTLs were induced, and the mice died of hemorrhagic ascites with Meth A cells and more acutely rejected RLmale1 cells. The CTLs on days 4-6 were inactive toward skin components at an in vivo effector/target ratio but injured endothelial cells to cause severe thrombosis/hemorrhage and more acute rejection of skin allografts. These results indicate that IFN-γ-dependent MMR expression was essential for macrophage-mediated cytolysis of allogeneic skin components and that IFN-γ-deficient mice more acutely rejected skin allograft by causing CTL-induced injury to endothelial cells.

Keywords: IFN-γ; T cell; allograft; macrophage; rodent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Endothelial Cells / immunology*
  • Graft Rejection / immunology*
  • Interferon-gamma / deficiency
  • Interferon-gamma / immunology*
  • Macrophages / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Skin / immunology*
  • T-Lymphocytes / immunology*
  • Transplantation, Homologous

Substances

  • IFNG protein, mouse
  • Interferon-gamma