Combination treatment with Anti-CD20 and oral Anti-CD3 prevents and reverses autoimmune diabetes

Hu, C, Ding, H, Zhang, X, Wong, Florence ORCID: https://orcid.org/0000-0002-2812-8845 and Wen, L 2013. Combination treatment with Anti-CD20 and oral Anti-CD3 prevents and reverses autoimmune diabetes. Diabetes 62 (8) , pp. 2849-2858. 10.2337/db12-1175

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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 preclinical evidence for the optimization of B cell-directed therapy for T1D.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	Animals;Antibodies, Monoclonal/pharmacology;Antibodies, Monoclonal/therapeutic use*;Antigens, CD20/immunology*; B-Lymphocytes/drug effects;B-Lymphocytes/immunology; CD3 Complex/immunology*;CD4-Positive T-Lymphocytes/drug effects;CD4-Positive T-Lymphocytes/immunology;CD4-Positive T-Lymphocytes/metabolism;Diabetes Mellitus, Type 1/drug therapy*;Interleukin-10/metabolism;Intestine, Small/drug effects;Intestine, Small/immunology;Intestine, Small/metabolism;Mice;Mice, Inbred NOD
Publisher:	American Diabetes Association
ISSN:	0012-1797
Last Modified:	23 Oct 2022 13:13
URI:	https://orca.cardiff.ac.uk/id/eprint/110035

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