Interest in regulatory T cells (Treg) has exploded since the discovery by Sakaguchi and colleagues of a minor population of CD4+ T
cells which expresses Foxp3 and plays a central role in the prevention of autoimmune reactions in vivo.'Natural Treg cells'
develop in the thymus, are present in naïve animals and their depletion causes the development of a spectrum of autoimmune disorders.
By contrast, 'adaptive or induced' Treg cells develop in peripheral lymphoid tissues. TGF-beta and IL-10 may be involved in the
conversion of T cells into CD4+ Foxp3+ displaying suppressive activity. Our laboratory has undertaken studies to evaluate the role
of natural Treg cells in the control of humoral and cellular responses.Our results show that thymicTreg cells exert a feedback
mechanism on antibody secretion by selectively dampening the T cell help for B cell activation, and downregulate activation of
Th1-type responses.The biological basis of Treg cell suppression is still elusive.Using various in vivo and in vitro models, we will
investigate the molecular mechanisms underlying their function, and in particular:'	Their capacity to inhibit dendritic cell function.
We recently found that Treg selectively inhibit thepro-Th1 CD70/CD27 pathway, while sparing interleukin 12 production. We will
analyze how the CD27 receptor inhibits CD70 expression on the plasma membrane of dendritic cells. Our data suggest that the CD27
receptor inhibits its own ligand, possibly by inducing its endocytosis in DCs, resulting in impaired Th1-prone CD70
costimulation.'	The role of CD27 on the development/function in vivoof Tregs (which express higher levels of CD27 than naïve T cells)in steady
state and inflammatory conditions'	The roleof the CD39-CD73 axis on the function of Tregswhich overexpress CD73, an
ecto-5'-nucleotidase acting in tandem with CD39 (an ecto-ATPase) to produce extracellular adenosine. This purine nucleoside has been shown to
inhibit T cell activation. We will analyze the function of the CD39 and CD73 receptors in the homeostasis of the intestinal tract.'	The
role of the negative receptor PD-1 on the function of Tregsin vivo, and in particular on their capacity to inhibit the
migration/function of effector T cells into the tumor bed, using the P815 mastocytoma of DBA/2 mice.