mhh, seminarroom 15.02.2010 14.30h. antigen + basophils + cd4 + t cells t h 2 cells il-4 fc ri mhc...
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Antigen + Basophils + CD4 + T cells T H 2 cells IL-4 Fc RI MHC IITRANSCRIPT
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MHH, Seminarroom
15.02.201014.30h
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Antigen + Basophils + CD4+ T cells TH2 cellsIL-4FcRI
MHC II
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• 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
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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
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Cytokine production of Basophils after Strongyloides infection in vitro
Basophils from infected mice produce large amounts of „TH2 cytokines“
Basophils + IL-3 (24h)
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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
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Ability of basophils to induce naive CD4+ T cells to develop into TH2 cells
without IL4
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without IL4
with IL4
Ability of basophils to induce naive CD4+ T cells to develop into TH2 cells
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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
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Bone marrow basophils induce TH2 cells in vitro
Expression of MHC II and costimulatory molecules
Bone marrow basophils express MHCII, CD80, CD86
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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
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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
-
+
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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
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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
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in vitro in vivo
Basophils are able to induce naive CD4+ cells to develop into
TH2 cells in vitro
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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
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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
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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
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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?
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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?
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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
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Thank you for your attention!