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Publication : Sub-optimal CD4+ T-cell activation triggers autonomous TGF-β-dependent conversion to Foxp3+ regulatory T cells.

First Author  Oliveira VG Year  2011
Journal  Eur J Immunol Volume  41
Issue  5 Pages  1249-55
PubMed ID  21469093 Mgi Jnum  J:175409
Mgi Id  MGI:5285493 Doi  10.1002/eji.201040896
Citation  Oliveira VG, et al. (2011) Sub-optimal CD4+ T-cell activation triggers autonomous TGF-beta-dependent conversion to Foxp3+ regulatory T cells. Eur J Immunol 41(5):1249-55
abstractText  Classical in vitro Treg conversion assays, which rely on optimal T-cell activation in the presence of exogenous TGF-beta, induce Foxp3 expression at a frequency far above that which is observed in vivo in Treg-dependent models of oral or transplantation tolerance. We have found that suboptimal murine T-cell activation in vitro results in induction of Foxp3 expression, in the absence of exogenous TGF-beta, at a frequency similar to that which we found in vivo upon anti-CD4-induced transplantation tolerance. We show that TCR triggering with either low-dose anti-CD3 or low-dose agonist peptide, as well as down-modulation of the TCR signal with non-depleting anti-CD4, promotes TGF-beta production by T cells, an event that precedes Foxp3 expression and is Foxp3 independent. These findings support the view that sub-immunogenic regimens lead to dominant tolerance as a result of T-cell intrinsic properties.
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