Prolonged survival in rat liver transplantation with mouse monoclonal antibody against an inducible costimulator (ICOS)

Transplantation. 2002 Apr 15;73(7):1027-32. doi: 10.1097/00007890-200204150-00003.

Abstract

Background: An inducible costimulator (ICOS), a recently identified costimulatory receptor with a close structural homology to CD28 and CTLA4, is expressed on activated T cells. Interaction with its ligand on antigen-presenting cells stimulates T-cell proliferation to produce a different spectrum of cytokine. The inhibition of ICOS-mediated signal transduction by an anti-ICOS antibody is considered to be capable of protecting against graft rejection in organ transplantation.

Methods: An anti-rat ICOS antibody was intravenously administered into recipients of dark Agouti-to-Lewis liver transplantations. The recipient lymphocytes from mesenteric lymph nodes were harvested on day 7 after transplantation for fluorescence-activated cell sorting analysis, and tissue specimens from the grafts were removed for histologic evaluation. Antigen-specific T-cell proliferation responses were assessed in vitro with anti-ICOS antibody.

Results: Monotherapy with the antibody significantly prolonged the graft survival time by inhibiting T-cell activation and its proliferation response. The graft-infiltrating cells, both CD4 and CD8 T cells, were not completely reduced even when rats were administered the antibody, whereas the expression of ICOS almost completely disappeared in these cells.

Conclusions: T-cell activation through the ICOS costimulatory pathway plays an important role in graft rejection, and manipulating its pathway is an effective method for modulating transplantation immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, Differentiation, T-Lymphocyte / physiology*
  • CD28 Antigens / physiology
  • Graft Survival*
  • Immunohistochemistry
  • Inducible T-Cell Co-Stimulator Protein
  • Liver Transplantation*
  • Lymphocyte Activation
  • Male
  • Mice
  • Rats
  • Rats, Inbred Lew
  • Receptors, Interleukin-2 / analysis
  • T-Lymphocytes / immunology
  • Transplantation, Homologous

Substances

  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte
  • CD28 Antigens
  • Icos protein, mouse
  • Icos protein, rat
  • Inducible T-Cell Co-Stimulator Protein
  • Receptors, Interleukin-2