title: Helper effector function of human T cells stimulated by anti-CD3 mAb can be enhanced by co-stimulatory signals and is partially dependent on CD40-CD40 ligand interaction.
abstract: In this study we have investigated whether anti-CD3-induced human T cell help for immunoglobulin production could be enhanced by co-stimulation of the T cells via other T cell surface molecules, and the contribution of CD40-CD40 ligand interaction to the execution of T helper effector function induced by these different stimulatory signals. In a system in which irradiated tonsillar T cells were stimulated with immobilized anti-CD3 monoclonal antibody (mAb), it was found that ligation of CD2 with a mitogenic pair of mAb considerably enhanced anti-CD3-induced T cell help for immunoglobulin production. Likewise, ligation of CD28 with mAb enhanced T helper activity, although to a lesser extent. Upon addition of anti-CD28 and anti-CD2 mAb together, an even higher immunoglobulin production was observed. This combination resulted in a four- to fivefold increase in immunoglobulin production as compared to cultures in which T cells were stimulated with anti-CD3 mAb alone. The effect of ligation with B7, the natural ligand of CD28, was studied in a system which utilizes the presentation of anti-CD3 mAb on human Fc gamma RII-expressing mouse fibroblasts which were co-transfected with human B7. It appeared that B7 could stimulate help for immunoglobulin production much more efficiently than ligation of CD28 with mAb did. Physical separation of B cells from T cells led to complete abrogation of immunoglobulin production. Blocking of CD40 with specific mAb, which have no intrinsic B cell stimulatory properties, or the CD40 ligand with a soluble CD40-human IgM fusion protein, resulted in dose-dependent, but only partial, inhibition of T cell-dependent immunoglobulin production with all modes of T cell activation tested. A clear correlation was found between the induction of CD40 ligand expression on the T cells by the different modes of co-stimulation and subsequent immunoglobulin production by the B cells. It is concluded that ligation of CD28 and/or CTLA-4, and of CD2 can generate co-stimulatory signals for T cell help for immunoglobulin production, which was found to be only partially dependent on the CD40-CD40 ligand interaction.
authors.affiliation: Laboratory of Cell Biology and Histology, University of Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Kwekkeboom
authors.forename: D
authors.initials: D
authors.lastname: de Rijk
authors.forename: A
authors.initials: A
authors.lastname: Kasran
authors.forename: S
authors.initials: S
authors.lastname: Barcy
authors.forename: C
authors.initials: C
authors.lastname: de Groot
authors.forename: M
authors.initials: M
authors.lastname: de Boer
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000917:Antibody Formation; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D018801:CD2 Antigens; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D019013:CD40 Antigens; D023201:CD40 Ligand; D016207:Cytokines / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D011971:Receptors, Immunologic / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D019013:CD40 Antigens; D016207:Cytokines; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D023201:CD40 Ligand