PTPN22 contributes to exhaustion of T lymphocytes during chronic viral infection

Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):E7231-E7239. doi: 10.1073/pnas.1603738113. Epub 2016 Oct 31.

Abstract

The protein encoded by the autoimmune-associated protein tyrosine phosphatase nonreceptor type 22 gene, PTPN22, has wide-ranging effects in immune cells including suppression of T-cell receptor signaling and promoting efficient production of type I interferons (IFN-I) by myeloid cells. Here we show that mice deficient in PTPN22 resist chronic viral infection with lymphocytic choriomeningitis virus clone 13 (LCMV cl13). The numbers and function of viral-specific CD4 T lymphocytes is greatly enhanced, whereas expression of the IFNβ-induced IL-2 repressor, cAMP-responsive element modulator (CREM) is reduced. Reduction of CREM expression in wild-type CD4 T lymphocytes prevents the loss of IL-2 production by CD4 T lymphocytes during infection with LCMV cl13. These findings implicate the IFNβ/CREM/IL-2 axis in regulating T-lymphocyte function during chronic viral infection.

Keywords: CREM; LCMV; PTPN22; T-cell exhaustion; chronic infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Cyclic AMP Response Element Modulator / immunology
  • Interferon Type I / immunology
  • Interleukin-10 / immunology
  • Lymphocytic Choriomeningitis / immunology*
  • Mice, Knockout
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22 / immunology*

Substances

  • Crem protein, mouse
  • IL10 protein, mouse
  • Interferon Type I
  • Interleukin-10
  • Cyclic AMP Response Element Modulator
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22
  • Ptpn22 protein, mouse