Direct reversal of the suppressive function of cd4+...

A - Human Necessities – 61 – K

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A61K 48/00 (2006.01)

Patent

CA 2600440

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 .

L'invention concerne les lymphocytes T régulateurs de CD4+ (Treg) qui inhibent profondément les réponses immunitaires d'un hôte et protègent ainsi contre les maladies auto-immunes tout en restreignant les réponses immunitaires désirées, telles que l'immunité antitumeur. Des oligonucléotides protégés par un phosphorothioate synthétique et contenant une guanosine peuvent inverser directement l'activité inhibitrice des lymphocytes Treg sans impliquer de cellules dendritiques. Cet effet donne l'impression d'être transduit par signalisation via le récepteur 8 de typeToll (TLR) et l'engagement des molécules MyD88 et IRAK4 dans des lymphocytes Treg. La stimulation des lymphocytes Trek à l'aide de ligands naturels pour TLR8 humains reprend l'effet des oligonucléotides contenant une guanosine synthétique.

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