Contribution of CD40-CD154-mediated costimulation to an alloresponse in vivo

Transplantation. 1999 May 15;67(9):1284-7. doi: 10.1097/00007890-199905150-00016.

Abstract

Background: Costimulation through CD40-CD154 plays an important role in T-cell activation. Although systemic administration of anti-CD154 antibody prevents or delays rejection of organ allografts in animal models, the molecular mechanisms responsible for this effect are not well defined.

Methods: We have previously demonstrated that priming of mice (H2d) with CD40-/- but not with wildtype naive B cells (H2b) leads to alloantigen-specific T-cell hyporesponsiveness in vitro. In the present study, we investigated whether such priming modifies allograft rejection in a major histocompatibility complex-mismatched murine cardiac transplantation model.

Results: Priming of hosts with donor-specific CD40-/- B cells delayed rejection of subsequently transplanted wild-type cardiac allografts by 8.0 days (P<0.001). The lack of CD40 on the cardiac graft delayed rejection in unprimed or primed hosts by 3-5 days. Prolongation of graft survival correlated with the failure of infused CD40-/- B cells to express B7.2 and ICAM-1 in vivo.

Conclusions: Our data suggest that CD40-CD154 costimulation contributes to T cell priming to alloantigens in vivo and to a second set rejection phase in which donor antigens are presented to primed T cells.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • B-Lymphocytes / immunology
  • B7-1 Antigen / immunology
  • CD40 Antigens / biosynthesis
  • CD40 Antigens / immunology*
  • CD40 Ligand
  • Epitopes, T-Lymphocyte / immunology
  • Graft Rejection / immunology*
  • Graft Rejection / prevention & control
  • Graft Survival / immunology
  • Heart Transplantation / immunology*
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Isoantibodies / biosynthesis*
  • Isoantigens / immunology
  • Lymphocyte Activation / immunology
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • T-Lymphocytes / immunology

Substances

  • B7-1 Antigen
  • CD40 Antigens
  • Epitopes, T-Lymphocyte
  • Isoantibodies
  • Isoantigens
  • Membrane Glycoproteins
  • Intercellular Adhesion Molecule-1
  • CD40 Ligand