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

Gyu Jin Lee, Yukyung Jun, Yoon Kyung Jeon, Daekee Lee, Sanghyuk Lee, Jaesang Kim

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish
Article number2015170
JournalOncoImmunology
Volume11
Issue number1
DOIs
StatePublished - 2022

Bibliographical note

Publisher Copyright:
© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.

Keywords

  • AITL
  • ATLL
  • CD28
  • CTLA4
  • fusion gene
  • murine model

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