+/- antigen specific T cells

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Presentation transcript:

+/- antigen specific T cells A) Antigen targeting to murine DC subpopulations induces different T cell responses in vivo CD8+ T cells CD11c+CD8+ Lehmann et al., Vaccines, 2016 Heidkamp et al., Encycl. of Cell Biology, 2016 Neubert et al., JI, 2014 Eissing et al., Immunoly Letters, 2014 Milo et al., Blood, 2013 Lindmark et al., JAutoimmun, 2012 Loschko et al., JI, 2011-2 Loschko et al., JI, 2011-1 O’Kamphorst et al., JI, 2010 Do et al., EJI, 2010 Yamazaki and Dudziak, JI, 2008 Dudziak et al., Science, 2007 Soares et al., JEM, 2007 Shakhar et al., Nat. Immunol. 2005 Lindquist et al., Nat. Immunol., 2004 DEC205-Ova B220 DEC205 DCIR2 CD4+ T cells CD11c+CD8- Spleen DCIR2-Ova (33D1) 1. Tumor responses? 2. APC presentation? 3. Stimulations differences? 4. Human? B) Antigen presented by DC subpopulations leads to differentiation and expansion of antigen specific regulatory T cells in the steady state in vivo Overview adapted from Gorelik and Flavell, Nat. Rev. Immunol, 2002 1. Direct effect of TGF-β on self-reactive T cell 2. Indirect effect of TGF-β via Treg cells 3. Generation of regulatory DC via Treg cells TGF-b TGF-β -BP2 TGF-β Receptor 1 SMAD1 SMAD4 CD8– CD8+ 2 SpDC PBS 33D1-OVA DEC-OVA CFSE FoxP3 0.25 2.0 95 3.0 2.5 0.26 97 4.5 16 22 58 CD4+CD25- T cells → CD4+CD25+FoxP3+ Treg Dependend on CD8+ DCs, TGF-β Expansion of FoxP3+ T cells by CD8- DCs FoxP3+ expansion FoxP3- FoxP3+ TGF-β CD8+ DCs CD8- DCs 5. Differentiation of CD4+ naïve T cells into Treg cells by simultaneous antigen presentation and secretion of TGF-β by CD8+DCs 6. Expansion of Treg cells by antigen presenting CD8- DCs (maybe also induction of regulatory DC) Yamazaki, Dudziak et al., et al., JI, 2008 Experimental Design TLR-Ligand C57BL/6 WT CD11c-YFP TLR-/-, MyD88-/- CD11c+CD8+ CD11c+CD8- pDC OT-I, OT-II In vitro In vivo microarray and miRNA protein changes (WB) DC migration (Immunfluorescence, 2- Photon) T cell proliferation (in vivo und in vitro) memory (in vivo und in vitro) antigen processing machinery Injection of TLR-ligands +/- antigen specific T cells Immature DC Mature DC C) Molecular analysis of DC subpopulations and their interacting T cells B220/DCIR2/DEC205 B T Baranska et al., in preparation