Transcript Ability of basophils to induce naive CD4 + T cells to develop into

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!