| First Author | Hu C | Year | 2013 |
| Journal | Diabetes | Volume | 62 |
| Issue | 8 | Pages | 2849-58 |
| PubMed ID | 23447122 | Mgi Jnum | J:208975 |
| Mgi Id | MGI:5565450 | Doi | 10.2337/db12-1175 |
| Citation | Hu C, et al. (2013) Combination treatment with anti-CD20 and oral anti-CD3 prevents and reverses autoimmune diabetes. Diabetes 62(8):2849-58 |
| abstractText | Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease, although B cells also play an important role in T1D development. Both T cell- and B cell-directed immunotherapies have shown efficacy in the prevention and reversal of T1D. However, whether the combined strategy of targeting both T and B cells could further improve therapeutic efficacy remains to be explored. We show that combined treatment with intravenous antihuman CD20 (hCD20) and oral anti-CD3 significantly delays diabetes development in prediabetic hCD20 transgenic NOD mice. More importantly, the combined treatment reverses diabetes in >60% of mice newly diagnosed with diabetes. Further mechanistic studies demonstrated that the addition of oral anti-CD3 to the B-cell depletion therapy synergistically enhances the suppressive function of regulatory T cells. Of note, the oral anti-CD3 treatment induced a fraction of interleukin (IL)-10-producing CD4 T cells in the small intestine through IL-10- and IL-27-producing dendritic cells. Thus, the findings demonstrate that combining anti-CD20 and oral anti-CD3 is superior to anti-CD20 monotherapy for restoring normoglycemia in diabetic NOD mice, providing important preclinical evidence for the optimization of B cell-directed therapy for T1D. |
