Depletion of IL‐2 receptor β‐positive cells protects from diabetes in non‐obese diabetic mice

• Published in: Immunology and cell biology 2016-02, Vol.94 (2), p.177-184
• Main Authors: Brauner, Hanna, Hall, Håkan T, Flodström‐Tullberg, Malin, Kärre, Klas, Höglund, Petter, Johansson, Sofia
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - administration & dosage; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cytotoxicity, Immunologic - drug effects; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - therapy; Female; Humans; Immunotherapy - methods; Insulin-Secreting Cells - immunology; Interleukin-2 Receptor beta Subunit - metabolism; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Lymphocyte Depletion; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Mice, Inbred NOD
• ISSN: 0818-9641; 1440-1711; 1440-1711
• DOI: 10.1038/icb.2015.78

The destruction of β‐cells in type 1 diabetes (T1D) progresses silently until only a minor fraction of the β‐cells remain. A late acting therapy leading to the prevention of further β‐cell killing would therefore be desirable. CD122, the β chain of the interleukin‐2 receptor, is highly expressed on natural killer (NK) cells and on a subpopulation of CD8 T cells. In this study, we have treated non‐obese diabetic (NOD) mice with a depleting antibody against CD122. The treatment protected from diabetes, even when initiated just before disease onset. The degree of leukocyte infiltration into islets was unaffected by the treatment, further supporting effectiveness late in the disease process. It effectively removed all NK cells from the spleen, pancreas and pancreatic lymph nodes and abolished NK cell activity. Interestingly, despite the lack of CD122 expression on CD8 T cells in the pancreas, the overall frequency of CD8 cells decreased in this organ, whereas it was unaffected in the spleen. T cells were also still capable to respond against a foreign antigen. Conclusively, targeting of CD122+ cells could represent a novel treatment strategy against T1D.