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Oncogene-specific T cells fail to eradicate lymphoma-initiating B cells in mice

Item Type:Article
Title:Oncogene-specific T cells fail to eradicate lymphoma-initiating B cells in mice
Creators Name:Hoser, D. and Schön, C. and Loddenkemper, C. and Lohneis, P. and Kühl, A.A. and Sommermann, T. and Blankenstein, T. and Willimsky, G.
Abstract:To date, little is known about the interaction between (pre-)malignant B cells and T cells. We generated transgenic mice that allow B cell-specific induction of the oncogene SV40 large T-antigen (TAg) to analyze the role of oncogene-specific T cells during sporadic B cell lymphoma development. Constitutive TAg expression in CD19-Cre x LoxP Tag mice resulted in TAg-tolerant CD8(+) T cells and development of B cell lymphomas. In contrast, CD19 CreER(T2) x LoxP Tag mice retained TAg-competent CD8(+) T cells at time of oncogene induction and TAg expression in few B cells of adult mice resulted in exceptionally rare lymphoma formation late in life. Increased lymphoma incidence in the absence of TAg-specific T cells suggested T cell-mediated inhibition of lymphoma progression. However, TAg-initiated B cells were not eliminated by T cells and detected long-term. Our results demonstrate a failure of the immune system to eradicate lymphoma-initiating B cells, retaining the risk of lymphoma development.
Keywords:B-Cell Lymphoma, B-Lymphocytes, CD8-Positive T-Lymphocytes, Cellular Immunity, Knockout Mice, Polyomavirus Transforming Antigens, Animals, Mice
Source:Blood
ISSN:0006-4971
Publisher:American Society of Hematology
Volume:132
Number:9
Page Range:924-934
Date:30 August 2018
Official Publication:https://doi.org/10.1182/blood-2018-02-834036
PubMed:View item in PubMed

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