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MHH, Seminarroom FceRI IL-4 Antigen + Basophils + CD4+ T cells TH2 cells MHC II Basophils • representing less than 1% of circulating white blood cells • susceptible to staining by base dyes • Basophils appear in many specific kinds of inflammatory reactions • can be found in unusually high numbers at sites of ectoparasite infection (e.g. ticks) • basophils are primary effector cells in allergic disorders Splenic Basophils in Strongyloides venezuelensis infected mice Strongyloides venezuelensis FceRI+ c-Kit - = Basophils FceRI+ c-Kit + = Mast cells Higher percentages of Basophils in Strongyloides venezuelensis infected mice Baophils (0.2% naive, 5.84% inf.) Mastcells (0.02%naive, 0.39% inf.) Cytokine production of Basophils after Strongyloides infection in vitro Basophils + IL-3 (24h) Basophils from infected mice produce large amounts of „TH2 cytokines“ MHC II expression on Basophils Same amount of MHCII expression on Basophils of naive and infected mice= MHCII expression is no limiting factor for TH2 induction Ability of basophils to induce naive CD4+ T cells to develop into TH2 cells without IL4 Ability of basophils to induce naive CD4+ T cells to develop into TH2 cells without IL4 with IL4 Ability of basophils to induce naive CD4+ T cells to develop into TH2 cells without IL4 with IL4 Basophils from infected mice are able to induce TH2 development without IL4 Bone marrow basophils induce TH2 cells in vitro Expression of MHC II and costimulatory molecules Bone marrow basophils express MHCII, CD80, CD86 Bone marrow basophils induce TH2 cells in vitro Basophils of wt mice of IL4-/- mice (G4/G4) without IL4 with IL4 Basophils of wt mice are able to induce naive CD4+ cells to develop into TH2 cells Basophils produce sufficient IL-4 for maximum development of TH2 cells Basophils pulsed with antigen-IgE complexes are potent APCs Basophils + DNP-OVA + CD4+ T cells TH2 cells Basophils are able to process DNP-OVA into OVA(323– 339) and to display peptide fragment in association with MHC class II and to produce IL-4 Basophils + DNP-OVA + IgE anti DNP + CD4+ T cells TH2 cells - + The enhancing effect of IgE anti-DNP on basophilinduced TH2 cell development was most apparent when basophils were pulsed with low concentrations of DNP-OVA Proliferation assay of CD4+ T cells CD4+ T cells + OVA or DNP-OVA +/- IgE anti-DNP of DNP-OVA These results suggest that basophils, taking advantage of their expression of FceRI, might efficiently take up low doses of antigen in an IgE-dependent way APC activity of basophils and sorted CD11c+ splenic DCs by changing the ratio of APCs to naive CD4+ T cells In presence of IgE-complex even low ratios of basophils induce TH2 development Basophils are able to induce naive CD4+ cells to develop into TH2 cells in vitro in vitro in vivo OVA-pulsed basophils induce TH2 cells in vivo Basophils + DNP-OVA + IgE anti DNP mice + challenge with OVA CD4+ T cells + OVA-pulsed DT–spleen cells Basophils induce TH2 development in vivo OVA-pulsed basophils induce TH2 cells in vivo Basophils + DNP-OVA + IgE anti DNP mice + challenge with OVA CD4+ T cells + OVA-pulsed DT–spleen cells Basophils induce TH2 development in vivo DCs induce TH1 but not TH2 development in vivo OVA-pulsed basophils induce TH2 cells in vivo Does OVA-pulsed basophils induce IgE and IgG1 production? Basophils + OVA mice OVA-pulsed basophils induce IgE and IgG1 production Basophils are important to induce TH2 responses in vivo Intravenous administration of antigen-IgE complex induces TH2 responses What happens aftre depletion of basophils? Basophils efficiently take up IC and induce TH2 development in vivo IC = Immune Complex (DNP-OVA + IgE anti DNP) MAR-1 = anti-FceRIa Depletion of Basophils blocks TH2 development and therefore IgG1 production of B cells Intravenous administration of antigen-IgE complex induces TH2 responses Does IL-3 administration increases the number of basophils? Yes, it does! Influence on Antibody production? Higher numbers of basophils lead to increased production of IgE and IgG1 Summary Basophils produce large amounts of „TH2 cytokines“ IL-4 and IL-13 after uptake of antigen Basophils are potent APCs Basophils are able to induce naive CD4+ cells to develop into TH2 cells Intravenous administration of antigen-IgE complex induces TH2 responses in vivo FceRI IL-4 Antigen + Basophils + CD4+ T cells TH2 cells MHC II Thank you for your attention!