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Mice transgenic for human CTLA4-CD28 fusion gene show proliferation and transformation of ATLL-like and AITL-like T cells

Title
Mice transgenic for human CTLA4-CD28 fusion gene show proliferation and transformation of ATLL-like and AITL-like T cells
Authors
Lee G.J.Jun Y.Jeon Y.K.Lee D.Lee S.Kim J.
Ewha Authors
이상혁김재상이대기
SCOPUS Author ID
이상혁scopus; 김재상scopus; 이대기scopus
Issue Date
2022
Journal Title
OncoImmunology
ISSN
2162-4011JCR Link
Citation
OncoImmunology vol. 11, no. 1
Keywords
AITLATLLCD28CTLA4fusion genemurine model
Publisher
Taylor and Francis Ltd.
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
CTLA4-CD28 gene fusion has been reported to occur in diverse types of T cell lymphoma. The fusion event is expected to convert inhibitory signals to activating signals and promote proliferation and potentially transformation of T cells. To test the function of the CTLA4-CD28 fusion gene in vivo, we generated a murine model that expresses the gene in a T cell-specific manner. The transgenic mice have shorter life spans and display inflammatory responses including lymphadenopathy and splenomegaly. T cells in turn show higher levels of activation and infiltrate various organs including the lung and skin. T cells, in particular CD4+ helper T cells, were also readily transplantable to immunocompromised mice. Transcriptomic profiling revealed that the gene expression pattern in CD4 + T cells closely resembles that of adult T cell leukemia/lymphoma (ATLL) and that of angioimmunoblastic T cell lymphoma (AITL) tissues. Consistently, we detected supernumerary FOXP3+ cells and PD-1+ cells in transgenic and transplanted mice. This is the first report demonstrating the transforming activity of the CTLA4-CD28 fusion gene in vivo, and this murine model should be useful in dissecting the molecular events downstream to this mutation. © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.
DOI
10.1080/2162402X.2021.2015170
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자연과학대학 > 생명과학전공 > Journal papers
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