| First Author | Tsai S | Year | 2010 |
| Journal | Immunity | Volume | 32 |
| Issue | 4 | Pages | 568-80 |
| PubMed ID | 20381385 | Mgi Jnum | J:179859 |
| Mgi Id | MGI:5304255 | Doi | 10.1016/j.immuni.2010.03.015 |
| Citation | Tsai S, et al. (2010) Reversal of autoimmunity by boosting memory-like autoregulatory T cells. Immunity 32(4):568-80 |
| abstractText | Blunting autoreactivity without compromising immunity remains an elusive goal in the treatment of autoimmunity. We show that progression to autoimmune diabetes results in the conversion of naive low-avidity autoreactive CD8(+) T cells into memory-like autoregulatory cells that can be expanded in vivo with nanoparticles coated with disease-relevant peptide-major histocompatibility complexes (pMHC-NP). Treatment of NOD mice with monospecific pMHC-NPs expanded cognate autoregulatory T cells, suppressed the recruitment of noncognate specificities, prevented disease in prediabetic mice, and restored normoglycemia in diabetic animals. pMHC-NP therapy was inconsequential in mice engineered to bear an immune system unresponsive to the corresponding epitope, owing to absence of epitope-experienced autoregulatory T cells. pMHC-NP-expanded autoregulatory T cells suppressed local presentation of autoantigens in an interferon-gamma-, indoleamine 2,3-dioxygenase-, and perforin-dependent manner. Nanoparticles coated with human diabetes-relevant pHLA complexes restored normoglycemia in a humanized model of diabetes. These observations expose a paradigm in the pathogenesis of autoimmunity amenable for therapeutic intervention. |
