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  • Title: Sub-optimal CD4+ T-cell activation triggers autonomous TGF-β-dependent conversion to Foxp3+ regulatory T cells.
    Author: Oliveira VG, Caridade M, Paiva RS, Demengeot J, Graca L.
    Journal: Eur J Immunol; 2011 May; 41(5):1249-55. PubMed ID: 21469093.
    Abstract:
    Classical 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.
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