| First Author | Bhatt S | Year | 2015 |
| Journal | Exp Hematol | Volume | 43 |
| Issue | 4 | Pages | 277-85 |
| PubMed ID | 25534204 | Mgi Jnum | J:230274 |
| Mgi Id | MGI:5755910 | Doi | 10.1016/j.exphem.2014.12.001 |
| Citation | Bhatt S, et al. (2015) Hepatic stellate cell-conditioned myeloid cells provide a novel therapy for prevention of factor VIII antibody formation in mice. Exp Hematol 43(4):277-85 |
| abstractText | A major complication of factor VIII (F.VIII) infusion therapies for the treatment of hemophilia A is the formation of antibodies (inhibitors) against F.VIII, a T-cell-dependent, B-cell-mediated process. To date, attempts to inhibit formation of the inhibitors have been limited in success. We have shown that hepatic stellate cells (HSCs) promote the development of myeloid-derived suppressor cells (MDSCs). The HSC-induced MDSCs are potent regulators of T-cell and B-cell responses. Here we show that MDSCs can be propagated from hemophilia A mouse bone marrow cells in coculture with HSCs. These cells exhibit a suppressive phenotype and display a marked ability to inhibit T-cell proliferation induced by dendritic cells in response to F.VIII. MDSCs can also inhibit proliferation and activation of B cells stimulated by immunoglobulin M and interleukin 4. Administration of HSC-induced MDSCs induces CD4(+) T cell and B220(+) B-cell hyporesponsiveness to F.VIII and reduces inhibitor formation in hemophilia A mice. These results suggest that MDSCs could serve as a form of immunotherapy for preventing inhibitor formation via induction of immune tolerance. |
