biostudies-literatureTurner MSNCI NIH HHSNIGMS NIH HHS4895-903https://www.ebi.ac.uk/biostudies/studies/S-EPMC3142864biostudies-literatureUnknown183(8)The definitions of tolerogenic vs immunogenic dendritic cells (DC) remain controversial. Immature DC have been shown to induce T regulatory cells (Treg) specific for foreign and allogeneic Ags. However, we have previously reported that mature DC (mDC) prevented the onset of autoimmune diabetes, whereas immature DC (iDC) were therapeutically ineffective. In this study, islet-specific CD4(+) T cells from BDC2.5 TCR-transgenic mice were stimulated in the absence of exogenous cytokine with iDC or mDC pulsed with high- or low-affinity antigenic peptides and examined for Treg induction. Both iDC and mDC presenting low peptide doses induced weak TCR signaling via the Akt/mammalian target of rapamycin (mTOR) pathway, resulting in significant expansion of Foxp3(+) Treg. Furthermore, unpulsed mDC, bJournal of immunology (Baltimore, Md. : 1950)Dominant role of antigen dose in CD4+Foxp3+ regulatory T cell induction and expansion.PMC3142864R01 GM080398T32 CA082084-10R01 GM080398-03R01 GM080398-02T32 CA0820845T32CA82084-10Turner MSKane LPMorel PAfalseDominant role of antigen dose in CD4+Foxp3+ regulatory T cell induction and expansion.The definitions of tolerogenic vs immunogenic dendritic cells (DC) remain controversial. Immature DC have been shown to induce T regulatory cells (Treg) specific for foreign and allogeneic Ags. However, we have previously reported that mature DC (mDC) prevented the onset of autoimmune diabetes, whereas immature DC (iDC) were therapeutically ineffective. In this study, islet-specific CD4(+) T cells from BDC2.5 TCR-transgenic mice were stimulated in the absence of exogenous cytokine with iDC or mDC pulsed with high- or low-affinity antigenic peptides and examined for Treg induction. Both iDC and mDC presenting low peptide doses induced weak TCR signaling via the Akt/mammalian target of rapamycin (mTOR) pathway, resulting in significant expansion of Foxp3(+) Treg. Furthermore, unpulsed mDC, b2009-01-01T00:00:00Z2009 Oct2025-04-04T12:00:40.444Z2019-03-26T23:42:54ZS-EPMC31428641980151410.4049/jimmunol.0901459