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1. Personal Background Next EUTRAIN meeting venue? Bari Alessandra - PowerPoint PPT Presentation

1. Personal Background Next EUTRAIN meeting venue? Bari Alessandra Petrelli (ESR2) City of origin Bari, Italy Education MD degree, Universit Vita Salute San Raffaele, Milan, Italy (2007) Clinical Training - Specialization in Internal


  1. 1. Personal Background Next EUTRAIN meeting venue? Bari Alessandra Petrelli (ESR2) City of origin Bari, Italy Education MD degree, Università Vita Salute San Raffaele, Milan, Italy (2007) Clinical Training - Specialization in Internal Medicine, Dep. of Transplant Medicine, Ospedale San Raffaele, Milan (2008-2013) Research - Research Fellowship in Pediatric Immunology, Department of Nephrology, Training Childrens Hospital, Harvard Medical School, Boston, MA (2009-2010) - Research Fellowship in Immune Tolerance, Diabetes Research Institute, Ospedale San Raffaele, Milan (2011-2012) - PhD student in Infection & Immunity, UMC Utrecht (2013-present) Interests - Autoimmune (T1D, RA/JIA) and alloimmune response (organ and cell transplantation). I’m interested in understaning the mechanisms of T cell activation and Treg-mediated suppression with the ultimate goal to halt the immune response towards auto/allo-antigens.

  2. 2. Projects outline PROJECT 1 - Teff cells from the synovial fluid (SF) A p=0.01 Resistance Induction B p<0.0001 of JIA patients are resistant to 80 1:2 suppression ( Wehrens, Blood 2011) TNFα 1:8 TNFα IL-6 suppression (%) 60 IFNγ p=0.009 > - APC from the SF induce resistance 40 Teff SF to tolerance (Wehrens E, A&R, APC SF 20 2013) TNFα 0 Intrinsic 8 8 8 8 D D D D C C C C + + + + IFNγ IL-6 Resistance s / s / - - - Treg from the SF are functional d d 3 3 a D a D e C e C b b ( Wehrens E, Blood 2011, Haufe S, IL-6 A&R 2011) � in presence of PB- SF-JIA PB-JIA Impaired function? APC, are impaired (Nie H, Nat Med 2013) in absence of APC C PROJECT 2 100 p=0.007 PB-JIA % on CD45RA- cells SF-JIA - CD8 T cells are effectors in 80 p=0.002 autoimmune inflammation 60 - SFMC are enriched in PD1+CD8+ T cells (C). 40 - PD1+CD8+ T cells in the SF have a 20 mixed phenotype of exhausted/cytotoxic cells 0 CCR7+ CD127low CD27- CCR5+ CD62L+ PD1+ CTLA4 Confidential data

  3. 3. Plans for next year PROJECT 1 - cross-over experiements to define whether Tregs from the SF have impaired function in absence of APC Elucidate the mechanism of Teff cell resistance to suppresion. Is it only TNF α - - mediated or cell-to-cell contact has a role? - Potentially expand the conclusions to the site of inflammation of other autoimmune diseases (i.e pancreatic lymphnodes of T1D, IBD infiltrate, etc) PROJECT 2 - Phenotypic characterization of PD1+CD8+ T cells - Generation of PD1+ and PD1-CD8+ T cell clones from the PB and the SF of JIA patients to: evaluate cytokine production upon stimulation and proliferative response to PD1 triggering, studying PD1 signaling, test differential resistance to suppression, TRAINING - Attend the YIM (PReS) and present the preliminary data in Ljubljana (Sept. 2013) -Attend the FOCIS congress, Chicago 2014 -Collaborate with ESR 8, San Raffaele, Milan to generate single cell clones -Collaborate with ESR1, UMC Utrecht, to study molecular pathways of PD1+CD8+ T cells

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