Abstract
Abstract We recently found that lactoferrin (LF), like TGF-β1, enhanced Ag non-specific Foxp3+ iTreg differentiation and the two molecules synergized to express Foxp3. In the present study, we investigated effect of LF and TGF-β1 on Ag-specific Foxp3+ iTreg differentiation. Naïve CD4+ T cells isolated from OT-II mice were co-cultured with OVA323–339-loaded T cell-depleted splenocytes as APCs. OVA-specific Foxp3+ Treg population was increased by LF and TGF-β1 alone, and synergistically increased by combination of the two molecules. However, these increases were diminished by additional CD28 stimulation using anti-CD28 Ab. In parallel, blockade of B7 molecules using CTLA4-Ig markedly increased the Foxp3 expression. These results imply that lactoferrin alone or particularly along with TGF-β1 can cause naïve T cells to differentiate into Foxp3+ Tregs, greater under weak co-stimulatory signals.
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