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Datasets  >  signalling dataset  >  Effect of regulatory T cell...

Effect of regulatory T cells on the amplitude and polarisation of T cell responses

signalling dataset

Our data demonstrate that treatment of primed mice with intact anti-CTLA-4 antibodies induces the development of regulatory T cells expressing high levels of ICOS and producing IL-10. These regulatory T cells inhibit Th1 responses, in vitro and in vivo, and repress experimental intestinal inflammation, by a mechanism involving IL-10 and IDO. These ICOS+ regulatory T cells appear distinct from the naturally occurring regulatory T cells described above, suggesting that two populations can inhibit DC-induced Th1 responses in vivo. Experiments are under way to identify the respective role and the synergy of IL-10 and IDO in the down-regulation of inflammatory responses in vivo. We have demonstrated the major role of IL-10 and indoleamine 2, 3 dioxygenase. We are presently trying to identify the cells expressing IDO (dendritic cells or epithelial cells?), using chimeras (WT/IDO KO) and purification of various cell populations from the lamina propria from control versus treated mice.
Our recent results have also shown that ICOS+ regulatory T cells are present in the colon of untreated mice, but absent in axenic animals, suggesting that their development is dependent on the intestinal flora. We will complete our experiments to further test the role of CD70 in Th1 priming in the presence or absence of regulatory T cells, and try to identify the mechanism by which these cells may downregulate the CD70 pathway. We will also pursue our study to identify the cells expressing indoleamine 2,3 dioxygenase in the colon following anti-CTLA-4 treatment.

Recent reports have suggested that regulatory T cells may affect the phenotype, survival and function of dendritic cells.
We have therefore tested whether the enhanced Th1 response correlated with increased expression of costimulatory molecules or increased production of IL-12 by dendritic cells. Our data (in vitro and in vivo) clearly show that the phenotype of these cells was not changed in the absence of regulatory T cells and that IL-12 was not required for enhanced Th1 priming. Our preliminary results point to a role of CD70, a membrane-associated molecule of the tumor necrosis factor family.





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