Ptpn22−/−and Ptpn22R619Wmice accumulate Th1 cells with age or following chronic immune challenge. Skin draining lymph nodes of <4month (Young) and >12-month-old (Aged) (A) WT and Ptpn22−/− mice or (B) WT and Ptpn22R619W were assessed for intracellular IFNγ, IL-16, TNFα, and IL-4 cytokine production following 6 h PMA, Ionomycin and monensin stimulation, determined by intracellular flow cytometry. N = 4–5 mice per genotype/time point. (C, D) For collagen induced arthritis model WT and Ptpn22−/− mice were immunised with CII in CFA (immunised) and compared to unimmunised mice (control). (C) Day 96 lymph nodes were restimulated for 6 h with PMA, ionomycin and monensin for 6 h and expression of IFNγ, IL-17, and TNFα determined by intracellular flow cytometry. (D) Mean clinical score of WT and Ptpn22−/− immunised mice 0–96 days. N = 10 mice/group; bars represent mean + s.e.m. (A–C) Each point represents an individual mouse, bars represent mean ± s.e.m.; NS = not significant, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 by two-way ANOVA, applying Sidak's multiple comparisons test.