title: PTPN22 contributes to exhaustion of T lymphocytes during chronic viral infection.
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.
authors: Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA 92037.
authors: Christian J
authors: CJ
authors: Maine
authors: Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA 92037.
authors: John R
authors: JR
authors: Teijaro
authors: Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA 92037.
authors: Kristi
authors: K
authors: Marquardt
authors: Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA 92037 lsherman@scripps.edu.
authors: Linda A
authors: LA
authors: Sherman
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D051786:Cyclic AMP Response Element Modulator / Q000276:immunology; D007370:Interferon Type I / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D018345:Mice, Knockout; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics / Q000276:immunology*
chemical_list: C497411:Crem protein, mouse; C556062:IL10 protein, mouse; D007370:Interferon Type I; D016753:Interleukin-10; D051786:Cyclic AMP Response Element Modulator; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; C516766:Ptpn22 protein, mouse
keywords: CREM; LCMV; PTPN22; T-cell exhaustion; chronic infection