Cell Reports
Volume 32, Issue 4, 28 July 2020, 107957
Journal home page for Cell Reports

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

https://doi.org/10.1016/j.celrep.2020.107957Get rights and content
Under a Creative Commons license
open access

Highlights

  • PTPN2 deletion increases the expansion and survival of effector T cells

  • PTPN2-deficient CD8+ T cells expand 11-fold more efficiently upon activated T cell transfer

  • PTPN2 deletion permits the re-expansion of T cells with a terminal effector phenotype

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.

Keywords

Protein tyrosine phosphatase non‑receptor type 2 (PTPN2)
T cell memory
programmed T cell expansion
adoptive T cell transfer
immunotherapy
effector T cells
phosphoproteome
autoimmunity
GWAS
single point mutation

Cited by (0)

10

Present address: Sanofi Genzyme, Baar, Switzerland

11

Present address: Discovery Biology Division, Syngene International Ltd., 560099 Bengaluru, India

12

These authors contributed equally

13

Lead Contact