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Rosenmontag -Seminar. 15.02.2010. 14.30h. MHH, Seminarroom. IL-4. Fc e RI. Antigen + Basophils + CD4 + T cells T H 2 cells. MHC II. Basophils. representing less than 1% of circulating white blood cells susceptible to staining by base dyes - PowerPoint PPT Presentation
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MHH, SeminarroomMHH, Seminarroom
15.02.201014.30h
Antigen + Basophils + CD4+ T cells TH2 cellsIL-4FcRI
MHC II
• 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
Basophils
Splenic Basophils in Strongyloides venezuelensis infected mice
Higher percentages of Basophils in Strongyloides venezuelensis infected miceBaophils (0.2% naive, 5.84% inf.)Mastcells (0.02%naive, 0.39% inf.)
FcRI+ c-Kit - = Basophils
FcRI+ c-Kit + = Mast cells
Strongyloides venezuelensis
Cytokine production of Basophils after Strongyloides infection in vitro
Basophils from infected mice produce large amounts of „TH2 cytokines“
Basophils + IL-3 (24h)
Same amount of MHCII expression on Basophils of naive and infected mice=MHCII expression is no limiting factor for TH2 induction
MHC II expression on Basophils
Ability of basophils to induce naive CD4+ T cells to develop into TH2 cells
without IL4
without IL4
with IL4
Ability of basophils to induce naive CD4+ T cells to develop into TH2 cells
Basophils from infected mice are able to induce TH2 development without IL4
without IL4
with IL4
Ability of basophils to induce naive CD4+ T cells to develop into TH2 cells
Bone marrow basophils induce TH2 cells in vitro
Expression of MHC II and costimulatory molecules
Bone marrow basophils express MHCII, CD80, CD86
of IL4-/- mice (G4/G4)Basophils of wt mice
Basophils of wt mice are able to induce naive CD4+ cells to develop into TH2 cellsBasophils produce sufficient IL-4 for maximum development of TH2 cells
Bone marrow basophils induce TH2 cells in vitro
without IL4
with IL4
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
The enhancing effect of IgE anti-DNP on basophil-induced TH2 cell development was most apparent when basophils were pulsed with low concentrations of DNP-OVA
Basophils + DNP-OVA + IgE anti DNP + CD4+ T cells TH2 cells
-
+
CD4+ T cells + OVA or DNP-OVA +/- IgE anti-DNP
These results suggest that basophils, taking advantage of their expression of FcRI, might efficiently take up low doses of antigen in an IgE-dependent way
of
DNP-OVA
Proliferation assay of CD4+ T cells
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
in vitro in vivo
Basophils are able to induce naive CD4+ cells to develop into
TH2 cells in vitro
OVA-pulsed basophils induce TH2 cells in vivo
Basophils + DNP-OVA + IgE anti DNP mice + challenge with OVA
CD4+ T cells + OVA-pulsed T–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 T–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?
OVA-pulsed basophils induce IgE and IgG1 production
Basophils are important to induce TH2 responses in vivo
Basophils + OVA mice
Intravenous administration of antigen-IgE complex induces TH2 responses
IC = Immune Complex (DNP-OVA + IgE anti DNP)MAR-1 = anti-FcRI
Basophils efficiently take up IC and induce TH2 development in vivo
Depletion of Basophils blocks TH2 development and therefore IgG1 production of B cells
What happens aftre depletion of basophils?
Intravenous administration of antigen-IgE complex induces TH2 responses
Does IL-3 administration increases the number of basophils?
Higher numbers of basophils lead to increased production of IgE and IgG1
Yes, it does!
Influence on Antibody production?
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
Antigen + Basophils + CD4+ T cells TH2 cellsIL-4FcRI
MHC II
Thank you for your attention!