Accessory function of endothelial cells in anti-CD3-induced T-cell proliferation: synergism with monocytes.
Monoclonal antibodies to CD3 can induce proliferation of resting T cells. In vitro this effect is dependent on the presence of monocytes. They serve as accessory cells providing a co-stimulatory signal after cross-linking of the antibody-coated TcR/CD3 complex by the Fc receptor on the monocytes. We have studied whether endothelial cells can replace monocytes with regard to this function. Highly purified T-cell preparations were cultured in the presence of anti-CD3 antibody, purified monocytes, and human umbilical vein endothelial cells. Anti-CD3 and endothelial cells alone were unable to support T-cell proliferation, due to lack of FcR expression. Addition, however, of as few as 1000 FcR+ monocytes (0.8% of the number of T cells present) to a coculture of T cells and endothelial cells (EC) in the presence of soluble anti-CD3 resulted in a strong proliferation of T cells. When anti-CD3 was presented in an immobilized form (coated to the culture well or to Sepharose beads), or when phytohaemagglutinin was added to the culture as a cross-linking agent, EC could support T-cell proliferation in the absence of any monocytes. We conclude that EC by themselves cannot support the proliferation of pure T cells induced by soluble anti-CD3, but are potent generators of the co-stimulatory signal(s). They provide a suitable starting material to further define this co-stimulatory activity.
Westphal
J R
JR
Institute of Pathology, University Hospital Nijmegen, The Netherlands.
Tax
W J
WJ
Willems
H W
HW
Koene
R A
RA
Ruiter
D J
DJ
De Waal
R M
RM
D000938:Antigen-Presenting Cells / Q000276:immunology*; D000943:Antigens, Differentiation / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D017252:CD3 Complex; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology*; D011940:Receptor Aggregation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D011961:Receptors, Fc / Q000378:metabolism; D017452:Receptors, IgG; D013601:T-Lymphocytes / Q000276:immunology*
D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc; D017452:Receptors, IgG