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 BJ, Salerno E, Gala K, Pan M, Langer JA, Mostowski HS, Bauer S, Marti G, Li Y, Tsiagbe VK, and Raveche ES
- Subjects
- Age Factors, Animals, Antibodies blood, Antibodies immunology, Antibodies pharmacology, Antibodies, Antinuclear blood, Ascitic Fluid cytology, Ascitic Fluid immunology, Autoimmune Diseases pathology, B-Lymphocytes cytology, B-Lymphocytes drug effects, B-Lymphocytes immunology, Erythrocytes immunology, Forkhead Transcription Factors genetics, Immune Tolerance immunology, Interferon-alpha blood, Interferon-alpha pharmacology, Interferons genetics, Interferons pharmacology, Interleukin-10 blood, Interleukin-10 genetics, Interleukin-2 Receptor alpha Subunit immunology, Lymph Nodes cytology, Lymph Nodes immunology, Mice, Mice, Inbred C57BL, Mice, Inbred NZB, Poly I-C pharmacology, Spleen cytology, Spleen drug effects, Spleen immunology, T-Lymphocyte Subsets cytology, T-Lymphocyte Subsets drug effects, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, T-Lymphocytes, Regulatory cytology, T-Lymphocytes, Regulatory drug effects, T-Lymphocytes, Regulatory metabolism, ZAP-70 Protein-Tyrosine Kinase genetics, Autoimmune Diseases immunology, Autoimmunity immunology, Leukemia, B-Cell immunology, Leukemia, B-Cell pathology, T-Lymphocytes, Regulatory immunology
- 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-alpha 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-alpha, 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.
- Published
- 2009
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