title: Triggering of T cell proliferation through CD28 induces GATA-3 and promotes T helper type 2 differentiation in vitro and in vivo.
abstract: The relative contribution of T cell receptor-versus CD28-mediated signals in co-stimulation of resting CD4 T cells is thought to influence their functional differentiation towards T helper (Th) 1 versus Th2 subsets. We have used a conventional and a mitogenic CD28-specific monoclonal antibody to assess the effect of polyclonal T cell activation through CD28 alone on CD4 subset differentiation. In vivo, mitogenic but not conventional anti-CD28 induces massive lymphocytosis, the Th2 cytokines interleukin (IL)-4 and IL-10, and Th2-dependent immunoglobulin isotypes, most notably IgE. In vitro, it is shown that mitogenic anti-CD28 primes for IL-4-dependent induction of IL-4 expression much more efficiently than conventional co-stimulation. At the molecular level, we show for the first time that the activation of the "Th2 promoting" transcription factor GATA-3 requires co-stimulation by CD28 and is also induced by mitogenic anti-CD28 alone. We suggest that CD28-dependent induction of GATA-3 in concert with other transcription factors, which are preferentially induced by strong CD28-signals, primes CD4 T cells for IL-4-dependent Th2 differentiaton.
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Rodríguez-Palmero
authors.forename: T
authors.initials: T
authors.lastname: Hara
authors.forename: A
authors.initials: A
authors.lastname: Thumbs
authors.forename: T
authors.initials: T
authors.lastname: Hünig
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology*; D050990:GATA3 Transcription Factor; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology; D015534:Trans-Activators / Q000276:immunology*
chemical_list: D018106:CD28 Antigens; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; D015534:Trans-Activators