Journal article
PTPN2 Deficiency Enhances Programmed T Cell Expansion and Survival Capacity of Activated T Cells
Markus Flosbach, Susanne G Oberle, Stefanie Scherer, Jana Zecha, Madlaina von Hoesslin, Florian Wiede, Vijaykumar Chennupati, Jolie G Cullen, Markus List, Josch K Pauling, Jan Baumbach, Bernhard Kuster, Tony Tiganis, Dietmar Zehn
Cell Reports | CELL PRESS | Published : 2020
Abstract
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 s..
View full abstractGrants
Awarded by Swiss National Science Foundation (SNSF)
Awarded by German Research Foundation
Awarded by H2020 project RepoTrial
Awarded by Federal Ministry of Education and Research (BMBF) project CLINSPECT-M
Funding Acknowledgements
We thank M. Prlic for input, feedback, and suggestions; B. Dotterbock, W. Schmid, and C. Amette for technical assistance; and S. Schleicher and C. Lechner for animal husbandry. MEC.B7.SigOVA cells were kindly provided by S. Schoenberger (San Diego, CA, USA). Work in the D.Z. laboratory was supported by a European Research Council starting grant (ProtecTC) and subsequently by a European Research Council consolidator grant (ToCCaTa), by grants from the Swiss National Science Foundation (SNSF; CRSII3_160708, 310030E-16187, 51PHP0_157319, and PP00P3_144883) and the Swiss Vaccine Research Institute (SVRI), and by grants from the German Research Foundation (SFB1054 and SFB1371). Contributions by J.K.P. were funded by the Bavarian State Ministry of Science and the Arts in the framework of the Bavarian Research Institute for Digital Transformation (BIDT). Work in the T.T. laboratory is supported by the National Health and Medical Research Council (NHMRC) of Australia; T.T. is an NHMRC Principal Research Fellow. J.B. is grateful for financial support from the H2020 project RepoTrial (777111), Federal Ministry of Education and Research (BMBF) project CLINSPECT-M (grant 031 L0214A), and grants from the German Research Foundation (SFB1371). The work from J.Z. and B.K. was supported by the German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ).