Transplantation tolerance induced by CTLA4-Ig

Transplantation. 1994 Jun 27;57(12):1701-6.

Abstract

The rejection of the transplanted allograft is dependent on T cell activation, which requires T cell receptor engagement by antigen and costimulatory signals delivered by T cell surface molecules such as CD28. CTLA4-Ig is a fusion protein that has previously been shown to block the CD28-mediated costimulatory signal and inhibit immune responses in vitro and in vivo. In this report we show that treatment of the C3H/He recipient of a BALB/c vascularized cardiac allograft with a 12-day course of CTLA4-Ig produced indefinite graft survival (> 100 days) in the majority of recipients. In addition, these recipients demonstrated donor-specific transplantation tolerance when tested with donor-specific (BALB/c) and third-party (C57BL/10) skin grafts. These results demonstrate that CTLA4-Ig can induce transplantation tolerance in the adult murine cardiac allograft model.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abatacept
  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antigens, CD
  • Antigens, Differentiation / pharmacology*
  • CTLA-4 Antigen
  • Graft Survival / drug effects*
  • Heart Transplantation / immunology*
  • Humans
  • Immunoconjugates*
  • Immunoglobulin Heavy Chains / pharmacology
  • Immunosuppression / methods
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Recombinant Fusion Proteins / pharmacology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Time Factors
  • Transplantation, Homologous / immunology

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ctla4 protein, mouse
  • Immunoconjugates
  • Immunoglobulin Heavy Chains
  • Recombinant Fusion Proteins
  • Abatacept