Mechanisms of tolerance induction by a gene-transferred peptide-IgG fusion protein expressed in B lineage cells.

摘要: A gene therapy model has been designed to induce tolerance multiple epitopes expressed in-frame on a soluble IgG fusion protein scaffold. Tolerance the λ repressor cI sequence p1-102 or its immunodominant (p12-26, p73-88) can be elicited when bone marrow (BM) LPS blasts are transduced and injected into naive even primed recipients. To explore mechanism of tolerance, class II−/− (knockout, KO) BM cells were with p1-102-IgG transferred irradiated These failed challenge epitopes, whereas +/+ did. This supports importance II MHC tolerogenic APC rather than secretion representation in tolerogenesis. When from μMT KO mice transfected p12-26-IgG mice, these also an epitope. results suggest direct involvement B epitopes. IL-10 infected construct still tolerogenic. Importantly, anti-CTLA-4 injections reversed primed, but not naive, recipients blasts. data emphasize presentation, cell involvement, CTLA-4 engagement induction and/or maintenance tolerance.