1. Regulatory T cells as central regulators of both autoimmunity and B cell malignancy in New Zealand Black mice
- Author
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Scaglione, Brian J., Salerno, Erica, Gala, Kinisha, Pan, Manjing, Langer, Jerome A., Mostowski, Howard S., Bauer, Steven, Marti, Gerald, Li, Yu, Tsiagbe, Vincent K., and Raveche, Elizabeth S.
- Subjects
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T cells , *AUTOANTIBODIES , *AUTOIMMUNE diseases - Abstract
Abstract: Regulatory T cells (Tregs) play an important role in protection against autoimmune disease and are also known to be potent inhibitors of anti-tumor immune responses. The New Zealand Black (NZB) mouse is a murine model for both autoimmune diseases, since high levels of autoantibodies are present, and human CLL, due to the expansion of malignant B-1 cells. In this study, we examined the functional role of CD4+CD25+ Foxp3+ Tregs in these different manifestations. Flow cytometric analysis showed increased levels of Tregs in NZB mice compared to healthy C57Bl/6 controls. Aged NZB mice that have developed a B-1 cell malignancy identified as IgM+CD5+, have the most pronounced increase in Tregs. Ex vivo treatment of splenocytes from NZB mice with IFN-α resulted in a decrease in the frequency of Tregs and malignant B-1 cells. In vivo treatment of both NZB and C57Bl/6 mice with poly (I:C), a potent inducer of IFN-α, also led to a decrease in the levels of Tregs and malignant B-1 cells (NZB only) while amplifying autoimmune manifestations. These results indicate that while high levels of Tregs found in NZB mice might suppress a more severe autoimmune disease, they may also contribute to the development of the B cell malignancy. [Copyright &y& Elsevier]
- Published
- 2009
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