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

• 1. Personal Background

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 Training

• Research Fellowship in Pediatric Immunology, Department of Nephrology,

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.

Next EUTRAIN meeting venue? Bari

• 2. Projects outline
• Teff cells from the synovial fluid (SF)
• f JIA patients are resistant to

suppression (Wehrens, Blood 2011)

• APC from the SF induce resistance

to tolerance (Wehrens E, A&R, 2013)

• Treg from the SF are functional

(Wehrens E, Blood 2011, Haufe S, A&R 2011) in presence of PB- APC, are impaired (Nie H, Nat Med 2013) in absence of APC

b e a d s + C D 8 C D 3

• /

+ C D 8 b e a d s + C D 8 C D 3

• /

+ C D 8

20 40 60 80

1:2 1:8 SF-JIA PB-JIA suppression (%)

p=0.01 p<0.0001 p=0.009

A

>

APC SF Teff SF

IFNγ IFNγ TNFα TNFα TNFα IL-6 IL-6 IL-6

Resistance Induction Intrinsic Resistance Impaired function?

• CD8

T cells are effectors in autoimmune inflammation

• SFMC are enriched in PD1+CD8+ T

cells (C).

• PD1+CD8+ T cells in the SF have a

mixed phenotype

• f

exhausted/cytotoxic cells

B

CCR7+ CD127low CD27- CCR5+ CD62L+ PD1+ CTLA4 20 40 60 80 100

p=0.002 p=0.007

% on CD45RA- cells

C

PROJECT 1 PROJECT 2 Confidential data

PB-JIA SF-JIA

• 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 TNFα-

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)

• 3. Plans for next year
• 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, PROJECT 1 PROJECT 2 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