BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Talks.cam//talks.cam.ac.uk//
X-WR-CALNAME:Talks.cam
BEGIN:VEVENT
SUMMARY:Innate signals regulating the Th1 cell life cycle - Dr Claudia Kem
 per\, MRC Centre for Transplantation\, King’s College London\, Guy’s H
 ospital
DTSTART:20110202T163000Z
DTEND:20110202T173000Z
UID:TALK28476@talks.cam.ac.uk
CONTACT:Suzy Blows
DESCRIPTION:Control of IFN-g-secreting T helper (Th) 1 cells is vital for 
 the prevention of autoimmunity and immunopathology during infection. The c
 ytokine interleukin (IL)-10 is fundamental in the negative control of Th1 
 cells. IL-10-mediated Th1 regulation is achieved ‘extrinsically’ throu
 gh suppression by induced IL-10-secreting regulatory T cells (iTreg or Tr1
 ) and ‘intrinsically’ by a recently discovered negative feedback loop 
 working via the timely co-induction of IL-10 in addition to IFN-g during T
 h1 lineage differentiation. We identified the complement regulator CD46 as
  key receptor in regulating IFN-g and IL-10 production in TH1 cells. CD46 
 not only drives IFN-g production and effector function of human TH1 cells 
 but also induces the switch to IL-10 secretion and into the regulatory pha
 se in an IL-2-dependent fashion: In the presence of low IL-2 CD46 induces 
 almost exclusively IFN-g+ effector TH1 cells while high environmental IL-2
  then switches these cells from an IFN-g+/IL-10+ intermediate finally into
  IL-10+ T cells\, with both of the latter populations being suppressive. I
 mportantly\, this CD46-mediated switch is defective in rheumatoid arthriti
 s (RA) patients: T cells from these patients lack the IL-10+ cell subpopul
 ation\, produce up to 20 times more IFN-g compared to those from healthy i
 ndividuals and never enter the regulatory phase. Thus\, we hypothesize tha
 t innate CD46-transduced signals play a vital role in the induction and re
 solution of human TH1 responses and that disturbance in CD46 signals is as
 sociated with autoimmune disease states including at minimum RA. \nInducin
 g/abrogating IFN-γ to IL-10 switching in Th1 cells at will presents one o
 f the most tantalising prospects for developing novel therapeutics targeti
 ng Th1-mediated diseases – here will summarize our present knowledge of 
 the innate-driven molecular pathways regulating the expression of IFN-γ v
 s. IL-10 in Th1.
LOCATION:Lecture Theatre 1\, Department of Veterinary Medicine
END:VEVENT
END:VCALENDAR