• Vanessa G Oliveira, Marta Caridade, Ricardo S Paiva, Jocelyne Demengeot, and Luis Graca.
• Instituto de Medicina Molecular, Medical School of University of Lisbon, Lisbon, Portugal.
• Eur. J. Immunol. 2011 May 1; 41 (5): 1249-55.

AbstractClassical in vitro Treg conversion assays, which rely on optimal T-cell activation in the presence of exogenous TGF-β, 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-β, 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-β 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.Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

33 keywords...

hide…