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Diabetes 54:306-310, 2005
© 2005 by the American Diabetes Association, Inc.
Rapid Publications |
Antigen-Specific FoxP3-Transduced T-Cells Can Control Established Type 1 Diabetes
1 Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School (MHH), Hannover, Germany
2 Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
CD4+CD25+ T-cells can be used to interfere with spontaneous autoimmune diseases such as type 1 diabetes. However, their low frequency and often unknown specificity represent major obstacles to their therapeutic use. Here we have explored the fact that ectopic expression of the transcription factor Foxp3 can confer a suppressor phenotype to naïve CD4+ T-cells. We found that retroviral transduction of polyclonal CD4 T-cells with FoxP3 was not effective in interfering with established type 1 diabetes. Thus, more subtle and more organ-specific regulation might be required to prevent type 1 diabetes, as well as to avoid systemic immunosuppression. However, a single injection of 105 FoxP3-transduced T-cells with specificity for islet antigen stabilized and reversed disease in mice with recent-onset diabetes. By comparing FoxP3-transduced T-cells with various antigen specificities, it became clear that the in vivo effect correlated with specific homing to and activation in pancreatic lymph nodes and not with in vitro suppressor activity or cytokine production. Our results complement recent results on in vitro–amplified antigen-specific T-cells in ameliorating type 1 diabetes and suggest that FoxP3 transduction of expanded T-cells might achieve the same goal.
Address correspondence and reprint requests to Elmar Jaeckel, Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Carl Neuberg Str. 1, 30625 Hannover, Germany. E-mail: jaeckel_elmar{at}yahoo.com
Abbreviations: CFSE, 5,6-carboxyfluorescein diacetate-succinimidyl ester; eGFP, enhanced green fluorescent protein; IL, interleukin
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