title: TNF-alpha, not CD154 (CD40L), plays a major role in SEB-dependent, CD4(+) T cell-induced endothelial cell activation in vitro.
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.
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, New York, New York, 10032, USA.
authors.forename: D
authors.initials: D
authors.lastname: Baum
authors.forename: R
authors.initials: R
authors.lastname: Yaron
authors.forename: M J
authors.initials: MJ
authors.lastname: Yellin
mesh_terms: D000911:Antibodies, Monoclonal; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology*; D009500:Neutralization Tests; D011994:Recombinant Proteins; D018089:Superantigens / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D007371:Interferon-gamma