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- Title
Combination Treatment With Anti-CD20 and 0ral Anti-CD3 Prevents and Reverses Autoimmune Diabetes.
- Authors
Changyun Hu; Heyuan Ding; Xiaojun Zhang; F. Susan Wong; Li Wen
- Abstract
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 precllnical evidence for the optimization of B cell-directed therapy for T1D.
- Publication
Diabetes, 2013, Vol 62, Issue 8, p2849
- ISSN
0012-1797
- Publication type
Academic Journal
- DOI
10.2337/db12-1175