title: Sustained linked stimulation via CD3 and CD4 is required for the IL-4-independent development of IL-4 synthesizing CD4+ T cells.
abstract: Previous work has shown that CD4 engagement can promote the development of interleukin-4-producing cells from naive CD4+ T cells activated with anti-CD3 antibody and interleukin-2 in the absence of other exogenous signals, including interleukin-4 itself. When CD44low CD4+ T cells were activated with immobilized anti-CD3 antibody and interleukin-2, they proliferated and produced interferon-gamma but not interleukin-4. Co-immobilization of antibodies to CD3 and CD4 enhanced cell recoveries and induced interleukin-4 as well as interferon-gamma synthesis. Here we show that these effects of CD4 ligation were not observed when anti-CD4 antibody was replaced with another CD4 ligand, interleukin-16, or when the anti-CD3 and anti-CD4 antibodies were spatially separated by immobilization on different beads. Removal of the anti-CD4 antibodies within the first three days of stimulation also prevented the development of detectable interleukin-4-producing cells. The data suggest that interleukin-4-independent priming of interleukin-4-producing cells in this system requires sustained stimulation via both the T cell receptor and CD4 with close physical association between the ligands for these two receptors.
authors.affiliation: The Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Queensland 4029, Australia.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Komata
authors.forename: William W
authors.initials: WW
authors.lastname: Cruikshank
authors.forename: Anne
authors.initials: A
authors.lastname: Kelso
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D019410:Interleukin-16 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015704:CD4 Antigens; D019410:Interleukin-16; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D007371:Interferon-gamma