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. 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. 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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