Mice transgenic for human CTLA4-CD28 fusion gene show proliferation and transformation of ATLL-like and AITL-like T cells
- 주제(키워드) CTLA4 , CD28 , murine model , ATLL , AITL , fusion gene
- 주제(기타) Oncology
- 주제(기타) Immunology
- 설명문(일반) [Lee, Gyu Jin; Lee, Daekee; Lee, Sanghyuk; Kim, Jaesang] Ewha Womans Univ, Dept Life Sci, 52 Ewhayeodae Gil, Seoul 03760, South Korea; [Lee, Gyu Jin; Lee, Sanghyuk; Kim, Jaesang] Ewha Res Ctr Syst Biol, Seoul, South Korea; [Jun, Yukyung; Lee, Sanghyuk; Kim, Jaesang] Ewha JAX Canc Immunotherapy Res Ctr, Seoul, South Korea; [Jeon, Yoon Kyung] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul, South Korea; [Jeon, Yoon Kyung] Seoul Natl Univ, Canc Res Inst, Seoul, South Korea
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published
- 발행기관 TAYLOR & FRANCIS INC
- 발행년도 2022
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000190322
- 본문언어 영어
- Published As https://doi.org/10.1080/2162402X.2021.2015170
- PubMed https://pubmed.ncbi.nlm.nih.gov/35003894
초록/요약
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.
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