PTPN2 Deficiency Enhances Programmed T Cell Expansion and Survival Capacity of Activated T Cells

Cell Reports

Jana Zecha¹  Jolie G. Cullen²  Jan Baumbach³  Tony Tiganis⁴  Madlaina von Hoesslin⁵  Dietmar Zehn⁵  Vijaykumar Chennupati⁶  Josch K. Pauling⁷  Florian Wiede⁷  Markus Flosbach⁷  Stefanie Scherer⁷  Markus List⁸  Susanne G. Oberle⁸  Bernhard Kuster⁹ 

[1] Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland;Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia;Big Data in BioMedicine Group, Chair of Experimental Bioinformatics, TUM School of Life Sciences Weihenstephan, Technical University of Munich (TUM), Freising, Germany;Chair of Experimental Bioinformatics, TUM School of Life Sciences Weihenstephan, Technical University of Munich (TUM), Freising, Germany;Chair of Proteomics and Bioanalytics, TUM School of Life Sciences Weihenstephan, Technical University of Munich (TUM), Freising, Germany;Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia;Division of Animal Physiology and Immunology, TUM School of Life Sciences Weihenstephan, Technical University of Munich (TUM), Freising, Germany;Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland;ZD.B Junior Research Group LipiTUM, Chair of Experimental Bioinformatics, TUM School of Life Sciences Weihenstephan, Technical University of Munich (TUM), Freising, Germany;

关键词: Protein tyrosine phosphatase non‑receptor type 2 (PTPN2);    T cell memory;    programmed T cell expansion;    adoptive T cell transfer;    immunotherapy;    effector T cells;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Manipulating molecules that impact T cell receptor (TCR) or cytokine signaling, such as the protein tyrosine phosphatase non-receptor type 2 (PTPN2), has significant potential for advancing T cell-based immunotherapies. Nonetheless, it remains unclear how PTPN2 impacts the activation, survival, and memory formation of T cells. We find that PTPN2 deficiency renders cells in vivo and in vitro less dependent on survival-promoting cytokines, such as interleukin (IL)-2 and IL-15. Remarkably, briefly ex vivo-activated PTPN2-deficient T cells accumulate in 3- to 11-fold higher numbers following transfer into unmanipulated, antigen-free mice. Moreover, the absence of PTPN2 augments the survival of short-lived effector T cells and allows them to robustly re-expand upon secondary challenge. Importantly, we find no evidence for impaired effector function or memory formation. Mechanistically, PTPN2 deficiency causes broad changes in the expression and phosphorylation of T cell expansion and survival-associated proteins. Altogether, our data underline the therapeutic potential of targeting PTPN2 in T cell-based therapies to augment the number and survival capacity of antigen-specific T cells.

【 授权许可】

Unknown