Differences in the stimulating capacity of immobilized anti-CD3 monoclonal antibodies: variable dependence on interleukin-1 as a helper signal for T-cell activation.
Monoclonal antibodies to the CD3 antigen on human T lymphocytes have been shown to induce accessory cell-dependent T-cell activation. One function of the accessory cells is cross-linking of CD3 by Fc receptor-binding of the anti-CD3 antibodies. Whether additional accessory signals are still required when anti-CD3 is presented in immobilized form is controversial. In the present study we stimulated purified human T cells with several anti-CD3 monoclonal antibodies, which were immobilized by coating the culture wells with goat anti-mouse IgG. A first group of immobilized anti-CD3 antibodies (anti-Leu-4, UCHT1, anti-T3, WT32 and 64.1) induced vigorous T-cell proliferation in the complete absence of monocytes, even when anti-interleukin-1 beta antiserum was added to the cultures. Other immobilized anti-CD3 antibodies (OKT3, WT31) required interleukin-1 beta in order to induce T-cell proliferation. However, when OKT3 was immobilized by direct coating of the culture wells with OKT3, it was also able to induce accessory cell-independent production of interleukin-2 and T-cell proliferation. Interleukin-1 beta further enhanced the interleukin-2-dependent proliferative response and it could provide help to induce proliferation at doses of immobilized OKT3 which, by themselves, were insufficient for full T-cell activation. We conclude that the requirement for interleukin-1 beta to induce interleukin-2-dependent proliferation of T cells when stimulated with anti-CD3 antibodies is not absolute, but depends on the CD3 epitope recognized, on the way of antibody presentation, on the antibody concentration and on other, still undefined, characteristics of the monoclonal antibodies used.
Verwilghen
J
J
Department of Internal Medicine and Pathophysiology, Faculty of Medicine, University of Leuven, Belgium.
Baroja
M L
ML
Van Vaeck
F
F
Van Damme
J
J
Ceuppens
J L
JL
D000328:Adult; D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D017252:CD3 Complex; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D011948:Receptors, Antigen, T-Cell