DIRECT REVERSAL OF THE SUPPRESSIVE FUNCTION OF CD4+ REGULATORY T CELLS VIA TOLL-LIKE RECEPTOR 8 SIGNALING

摘要

CD4⁺ regulatory T (Treg) cells profoundly suppress host immune responses and thus protect against autoimmune disease while restricting desired immune responses such as antitumor immunity. Synthetic phosphorothioate-protected, guanosine-containing oligonucleotides can directly reverse the suppressive activity of Treg cells without involving dendritic cells. This effect appears to be transduced by signaling through Toll-like receptor (TLR) 8 and engagement of the MyD88 and IRAK4 molecules in Treg cells. Stimulation of Treg cells with natural ligands for human TLR8 recapitulated the effect of the synthetic guanosine-containing oligonucleotides .