title: Regulatory T cells as central regulators of both autoimmunity and B cell malignancy in New Zealand Black mice.
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.
authors.affiliation: University of Medicine and Dentistry, New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Scaglione
authors.forename: Erica
authors.initials: E
authors.lastname: Salerno
authors.forename: Kinisha
authors.initials: K
authors.lastname: Gala
authors.forename: Manjing
authors.initials: M
authors.lastname: Pan
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Langer
authors.forename: Howard S
authors.initials: HS
authors.lastname: Mostowski
authors.forename: Steven
authors.initials: S
authors.lastname: Bauer
authors.forename: Gerald
authors.initials: G
authors.lastname: Marti
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Vincent K
authors.initials: VK
authors.lastname: Tsiagbe
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Raveche
mesh_terms: D000367:Age Factors; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology / Q000494:pharmacology; D000974:Antibodies, Antinuclear / Q000097:blood; D001202:Ascitic Fluid / Q000166:cytology / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000235:genetics; D007108:Immune Tolerance / Q000276:immunology; D016898:Interferon-alpha / Q000097:blood / Q000494:pharmacology; D007372:Interferons / Q000235:genetics / Q000494:pharmacology; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D015448:Leukemia, B-Cell / Q000276:immunology* / Q000473:pathology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D011070:Poly I-C / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics
chemical_list: D000906:Antibodies; D000974:Antibodies, Antinuclear; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016898:Interferon-alpha; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10; D007372:Interferons; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse; D011070:Poly I-C