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SUMMARY:Positive and negative influences of regulatory T cells in generati
 ng the naïve T cell compartment - Dr Joanna Davies\, Torrey Pines Institu
 te\, California
DTSTART:20111117T123000Z
DTEND:20111117T133000Z
UID:TALK32731@talks.cam.ac.uk
CONTACT:Sue Griffin
DESCRIPTION:Mechanisms that control the size of the T cell pool\, the rati
 o between naïve cells and memory cells\, the number and frequency of regu
 latory T cells\, and T cell receptor (TCR) diversity are necessary to main
 tain immune integrity and avoid disease. \n\nWe have shown that a subset o
 f naïve CD4+ T cells\, defined by the expression on their surface of a ve
 ry low density of CD44 (CD44v.low cells) are extremely efficient in creati
 ng a T cell pool with a diverse TCR repertoire\, generating regulatory T c
 ells that express Foxp3\, and promoting a large naïve cell population tha
 t is present in homeostatic equilibrium with memory and Foxp3+ regulatory 
 T cell (Treg) numbers. The data support a key role for CD4+ CD44v.low cell
 s as peripheral precursors that maintain the integrity of the CD4+ T cell 
 pool. \n\nThis finding is significant because prior to this study\, it was
  a well-established paradigm that the naïve cell compartment could only b
 e generated by thymopoiesis. We further challenge that paradigm by showing
  that conventional naïve cells can also reconstitute a naïve cell compar
 tment in lymphopenic hosts by manipulating their composition of thymus-der
 ived natural nTregs and peripherally derived acquired aTregs. Thus\, the a
 bility of conventional naïve cells to repopulate the naïve cell compartm
 ent is negatively influenced by nTregs\, and\, in the absence of nTregs\, 
 positively influenced by aTregs. Mechanistic studies show alternative cyto
 kine pathways for Treg function in promoting and inhibiting naïve cell re
 constitution culminating in changes in the cell surface expression of CD44
  and the interleukin-7 receptor respectively. \n\nUnderstanding the appare
 ntly opposing roles of aTregs and nTregs in establishing and maintaining a
  functional CD4+ T cell compartment will be important in the design of the
 rapeutic strategies to establish or re-establish immune homeostasis in con
 ditions of lymphopenia and immune dysregulation\, respectively. \n
LOCATION:Lecture Theatre\, Department of Pathology\, Tennis Court Road
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