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

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.

Baum D ，Yaron R ，Yellin MJ 《CELLULAR IMMUNOLOGY》

Vbeta-restricted T cell adherence to endothelial cells: a mechanism for superantigen-dependent vascular injury.

Brogan PA ，Shah V ，Klein N ，Dillon MJ ... -  《ARTHRITIS AND RHEUMATISM》

Effect of human cytokines (IFN-gamma, TNF-alpha, IL-1 beta, IL-4) on porcine endothelial cells: induction of MHC and adhesion molecules and functional significance of these changes.

Batten P ，Yacoub MH ，Rose ML 《-》

Lymphocyte-mediated activation of cultured endothelial cells (EC). CD4+ T cells inhibit EC class II MHC expression despite secreting IFN-gamma and increasing EC class I MHC and intercellular adhesion molecule-1 expression.

Doukas J ，Pober JS 《JOURNAL OF IMMUNOLOGY》

Fas/Fas ligand interaction regulates cytotoxicity of CD4+ T cells against staphylococcal enterotoxin B-pulsed endothelial cells.

Urayama S ，Kawakami A ，Matsuoka N ，Tsuboi M ，Nakashima T ，Kawabe Y ，Koji T ，Eguchi K ... -  《BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS》