Endothelial cells promote anti-CD3-induced T-cell proliferation via cell-cell contact mediated by LFA-1 and CD2.
T-cell activation requires not only T-cell receptor (TCR) engagement and subsequent TCR/CD3 cross-linking, but also one or more secondary activation signals generated by accessory cells (AC). We investigated the accessory function of endothelial cells (EC) in an in vitro model for T-cell activation where the first cross-linking signal was delivered to peripheral human T lymphocytes by either immobilized anti-CD3 monoclonal antibody (MoAb) or by PHA. In a previous report, we showed that EC provided a potent costimulatory signal in this model system. We have now analysed the nature of the EC-derived costimulatory signal by testing whether EC could be substituted by cytokines, by studying the effect of EC fixation and by testing the involvement of a number of adhesion molecules. Our findings indicate that EC accessory function is mediated mainly by membrane-bound factors. The nature of these membrane-bound factors was analysed by studying the inhibitory properties of a series of MoAbs directed against several adhesion molecules. Antibodies directed against CD44, E-selectin, CD31, CD26, B7/BB1, VLA-4 or VCAM-1 were not inhibitory. However, an inhibition, was clearly observed with antibodies against LFA-1 and CD2. Remarkably, this inhibition was not found with MoAbs to their respective counterstructures ICAM-1 and LFA-3. In summary, we postulate that both LFA-1/ICAM-1, and CD2/LFA-3 interactions are involved in EC accessory function, although the role of the EC-associated adhesion partners is not fully understood.
Westphal
J R
JR
Department of Pathology, University Hospital Nijmegen, The Netherlands.
Willems
H W
HW
Tax
W J
WJ
Koene
R A
RA
Ruiter
D J
DJ
De Waal
R M
RM
D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018801:CD2 Antigens; D017252:CD3 Complex / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology; D002450:Cell Communication; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D005557:Formaldehyde; D006801:Humans; D007378:Interleukins / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D010835:Phytohemagglutinins; D011108:Polymers; D011971:Receptors, Immunologic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D016707:Tissue Fixation; D014471:Umbilical Veins
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D007378:Interleukins; D016169:Lymphocyte Function-Associated Antigen-1; D010835:Phytohemagglutinins; D011108:Polymers; D011971:Receptors, Immunologic; D005557:Formaldehyde; C003043:paraform