The role of regulatory T cells in the NZB disease (130.10)

Abstract

Abstract Regulatory T cells (Tregs) play an important role in protection against autoimmune disease. These CD4+ CD25+ Foxp3+ T cells are also known to be potent inhibitors of antitumor immune responses. The NZB mouse is a murine model for both autoimmune diseases such as SLE, since high levels of autoantibodies are present, as well as a model of human CLL, due to the expansion of malignant B-1 cells. In this study, we examined the role of Tregs in the onset of these disease manifestations. Flow cytometric analysis of spleen, lymph node, and peritoneal cells showed increased levels of CD4+ CD25+ Foxp3+ Tregs in 12 to17-month old NZB mice with a B cell malignancy identified by IgM+ CD5+ B220 dull cells as compared to healthy C57Bl/6 controls. Furthermore, ex vivo treatment of cells from these tissues with IFN-α, which has been known to increase autoimmune symptoms in NZB mice, led to a decrease in the levels of Tregs 48 hours post treatment. These results indicate that while the levels of Tregs found in NZB mice may suppress a more severe autoimmune disease, they might also contribute to the development of the B cell malignancy. (Funded in part by a grant from the Alliance for Lupus Research to JAL).