The role of Gr1+ cells after anti-CD20 treatment in type 1 diabetes in nonobese diabetic mice

• Published in: The Journal of immunology (1950) Vol. 188; no. 1; pp. 294 - 301
• Main Authors: Hu, Changyun, Du, Wei, Zhang, Xiaojun, Wong, F Susan, Wen, Li
• Format: Journal Article
• Language: English
• Published: United States 01.01.2012
• Subjects: Animals; Antibodies, Monoclonal, Murine-Derived - immunology; Antibodies, Monoclonal, Murine-Derived - pharmacology; Antigens, CD20 - immunology; B-Lymphocytes - immunology; B-Lymphocytes - pathology; CD11b Antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Cell Differentiation - immunology; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - pathology; Diabetes Mellitus, Type 1 - therapy; Humans; Immune Tolerance; Immunotherapy; Lymphocyte Depletion; Mice; Mice, Inbred NOD; Mice, Transgenic; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - pathology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1101590

Studies suggest that Gr1(+)CD11b(+) cells have immunoregulatory function, and these cells may play an important role in autoimmune diseases. In this study, we investigated the regulatory role of Gr1(+)CD11b(+) cells in protecting against type 1 diabetes in NOD mice. In this study, we showed that temporary B cell depletion induced the expansion of Gr1(+)CD11b(+) cells. Gr1(+)CD11b(+) cells not only directly suppress diabetogenic T cell function but also can induce regulatory T cell differentiation in a TGF-β-dependent manner. Furthermore, we found that Gr1(+)CD11b(+) cells could suppress diabetogenic CD4 and CD8 T cell function in an IL-10-, NO-, and cell contact-dependent manner. Interestingly, single anti-Gr1 mAb treatment can also induce a transient expansion of Gr1(+)CD11b(+) cells that delayed diabetes development in NOD mice. Our data suggest that Gr1(+)CD11b(+) cells contribute to the establishment of immune tolerance to pancreatic islet autoimmunity. Manipulation of Gr1(+)CD11b(+) cells could be considered as a novel immunotherapy for the prevention of type 1 diabetes.