title: Critical role of CD81 in cognate T-B cell interactions leading to Th2 responses.
abstract: We previously demonstrated that CD81-/- mice fail to develop Th2-biased immune responses and allergen-induced airway hyper-reactivity. Because CD81 is expressed on both activated T and on B cells, we examined the role of CD81 expression by each cell type. We established an in vitro system by backcrossing the CD81 deletion to TCR transgenic (Tg) mice and to BCR Tg mice. Here we demonstrate that CD81 expression by T cells is critical for their induction of IL-4 synthesis by B cells. CD81-/- TCR Tg T cells were impaired in IL-4 production compared to CD81+/+ TCR Tg T cells, whereas CD81-/- and CD81+/+ BCR Tg B cells induced equivalent amounts of IL-4 in CD81+/+ TCR Tg T cells. CD81-/- TCR Tg T cells expressed reduced levels of ICOS, GATA-3, STAT6 and phosphorylated STAT6 when activated by antigen-presenting B cells. Taken together, these results indicate that CD81 expression by T cells greatly enhances cognate T-B cell interactions and greatly augments intracellular activation pathways leading to Th2 polarization.
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University Medical Center, CA 94305, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Deng
authors.forename: Rosemarie H
authors.initials: RH
authors.lastname: Dekruyff
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Freeman
authors.forename: Dale T
authors.initials: DT
authors.lastname: Umetsu
authors.forename: Shoshana
authors.initials: S
authors.lastname: Levy
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D000954:Antigens, Surface / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D002448:Cell Adhesion; D002450:Cell Communication; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D050990:GATA3 Transcription Factor; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050800:STAT6 Transcription Factor; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D060225:Tetraspanin 28; D018418:Th2 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface; C554799:Cd81 protein, mouse; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D008565:Membrane Proteins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D060225:Tetraspanin 28; D015534:Trans-Activators; D015847:Interleukin-4