title: TCR-stimulated naive human CD4+ 45RO- T cells develop into effector cells that secrete IL-13, IL-5, and IFN-gamma, but no IL-4, and help efficient IgE production by B cells.
abstract: It is currently believed that IgE production by B cells is induced by activated CD4+ Th2-like cells that produce increased amounts of IL-4 but low levels of IFN-gamma. We found that "naive" CD4+ 45RO- T cells primed and restimulated in vitro via the TCR developed into effector cells that produced large amounts of IL-13, IL-5, and IFN-gamma, but no IL-4. Such CD4 T cells induced surface IgD+E- B cells to produce large amounts of IgE. The IgE response could be blocked completely by neutralizing anti-IL-13 Abs, whereas anti-IL-4 had no effect. Addition of exogenous IL-4 during priming of CD4 cells suppressed clonal expansion and the development of Th cells including helpers for IgE, but increased endogenous production of IL-4 and IL-5, and suppressed production of IFN-gamma. Addition of exogenous IFN-alpha, IFN-gamma, or neutralizing anti-IFN-gamma mAbs affected neither priming of CD4 T cells nor B cell help. In contrast to CD4+ 45RO- naive T cells, CD4+ 45RO+ "memory" T cells primed and restimulated in vitro secreted IL-4 in addition to IL-13, IL-5, and IFN-gamma, and the IgE response induced by such cells could be blocked only by a combination of anti-IL-4 plus anti-IL-13 Abs. Unlike CD4 cells, CD8 cells could not be primed to help IgE production. The results indicate that TCR/CD3 cross-linking on naive human CD4 T cells is sufficient to induce the development of potent IgE helper cells, which secrete large amounts of IL-13, IL-5, and IFN-gamma, but no IL-4. Such Th cells may exacerbate atopic inflammation, because all by themselves they could drive IL-13-dependent IgE production, IL-5-dependent eosinophilia, and IFN-gamma-dependent macrophage activation, but could not suppress IFN-gamma production by other T cells via IL-4.
authors.affiliation: Department of Asthma/Allergy Research, Ciba-Geigy Ltd., Basel, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Brinkmann
authors.forename: C
authors.initials: C
authors.lastname: Kristofic
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis*; D017493:Leukocyte Common Antigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D018793:Interleukin-13; D015848:Interleukin-5; D007378:Interleukins; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens