TNF-alpha, not CD154 (CD40L), plays a major role in SEB-dependent, CD4(+) T cell-induced endothelial cell activation in vitro

Cell Immunol. 1998 Nov 25;190(1):12-22. doi: 10.1006/cimm.1998.1380.

Abstract

CD4(+) T cell effector molecules, in particular TNF-alpha and CD154, activate endothelial cells. However, the relative contributions of TNF-alpha and CD154 in mediating endothelial cell activation during complex Ag-driven CD4(+) T cell-endothelial cell interactions are not known. We utilized an in vitro model of CD4(+) T cell-endothelial cell interactions to characterize the contributions of TNF-alpha and CD154 in mediating upregulation of adhesion molecules CD54, CD62E, and CD106 on human umbilical vein endothelial cells (HUVEC). HUVEC were first treated with IFN-gamma to upregulate MHC Class II expression. IFN-gamma minimally effects HUVEC adhesion molecule expression but renders them capable of MHC class II restricted interactions with CD4(+) T cells. Coculturing MHC class II+ HUVEC and CD4(+) T cells with the superantigen SEB induces a rapid and marked upregulation of CD54, CD62E, and CD106 expression on HUVEC, as shown by FACS analysis. To study the effector molecules mediating SEB-driven, CD4(+) T cell-dependent endothelial cell activation, similar experiments were performed in the presence of neutralizing anti-CD154, anti-TNF-alpha, or anti-IL1 antibodies, as well as combinations of these antibodies. In contrast to the anti-CD154 or anti-IL-1 antibodies, the anti-TNF-alpha mAb markedly inhibited SEB-dependent, CD4(+) T cell-induced HUVEC activation. We conclude that TNF-alpha, not CD154, plays the major role in SEB-driven, CD4(+) T cell-induced endothelial cell activation in vitro.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal
  • Antigen Presentation
  • CD4-Positive T-Lymphocytes / immunology*
  • CD40 Ligand
  • Cells, Cultured
  • Coculture Techniques
  • Down-Regulation
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / immunology*
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Immune Tolerance
  • Immunity, Cellular
  • Interferon-gamma / pharmacology
  • Interleukin-1 / immunology
  • Lymphocyte Activation
  • Membrane Glycoproteins / immunology*
  • Neutralization Tests
  • Recombinant Proteins
  • Superantigens / administration & dosage
  • Tumor Necrosis Factor-alpha / immunology*

Substances

  • Antibodies, Monoclonal
  • Histocompatibility Antigens Class II
  • Interleukin-1
  • Membrane Glycoproteins
  • Recombinant Proteins
  • Superantigens
  • Tumor Necrosis Factor-alpha
  • CD40 Ligand
  • Interferon-gamma