(data are shown as the mean SEM. diseases including type I diabetes, rheumatoid arthritis, and systemic lupus erythematosus, among others (24C26). Mice Show Improved Clearance of LCMV cl13 Contamination. To investigate whether the loss of PTPN22 promotes antiviral activity in chronic contamination, we infected and WT mice with 106 pfu of LCMV cl13 i.v. and decided viral titers in serum at the indicated time points (Fig. 1mice as compared with WT mice. By day 39 all mice had cleared the infection, whereas significant levels of virus persisted in all WT mice (Fig. 1mice, but not WT CH5138303 mice, regained the weight loss associated with LCMV cl13 contamination (Fig. 1mice by day 14, whereas WT mice had detectable virus in the spleen, lung, liver, and kidney at this time point (Fig. S1 and (= 10) and WT (= 10) mice were infected i.v. with 106 pfu of LCMV cl13, and serum was collected at the specified time points. (and and WT mice were injected with CD4-depleting antibody before contamination with LCMV cl13, and viral titer was measured in the serum ( 0.05; ** 0.01; *** 0.001. Open in a separate window Fig. S1. mice clear LCMV cl13 contamination (related to Fig. 1). (and and WT mice were infected with 106 pfu of LCMV cl13, and organ CH5138303 viral load was measured at day 8 (and WT mice were infected i.v. with 105 pfu of LCMV cl13, and serum was collected at the specified time points. Plaque assays were carried out to determine the viral titer in the serum. ND, not detected. The data in graphs are shown as the mean SEM. At a lower dose of LCMV cl13 (105 pfu) clearance was CH5138303 more rapid, and virus was undetectable in the serum as early as 14 d postinfection (Fig. S1mice during comparable levels of contamination, we chose to Rabbit polyclonal to TOP2B CH5138303 focus on the 106 pfu dose in future studies. Normally, functional CD4 cells are required for clearance of LCMV. However, because deficiency has been reported to enhance CD8 function (27, 31), it was of interest to determine whether mice, we injected a group of mice with CD4-depleting antibody (Fig. 1 and group treated with CD4-depleting antibody, LCMV cl13 persistence was comparable to that in WT mice, suggesting that CD4 T cells are necessary for the viral CH5138303 clearance mechanism in mice. PTPN22 Is Necessary for Efficient IFN-I Production During LCMV cl13 Contamination. IFN-I is produced rapidly and in large quantities immediately following LCMV cl13 contamination and recently has been found to contribute to T-cell exhaustion and viral persistence (21, 22). Because PTPN22 affects the level of IFN-I production by myeloid cells, we investigated this pathway following LCMV cl13 contamination. Twenty-four hours after contamination with LCMV cl13 the frequency of IFN-producing pDCs was reduced significantly (50%) in spleen cells from mice as compared with WT mice (Fig. 2 and mice compared with WT mice (Fig. 2 and and show combined data from two impartial experiments combined, each symbol represents one mouse. (and and are two independent experiments. Each bar has four data points; each point is usually representative of two pooled mouse spleens. The data in graphs are shown as the mean SEM; * 0.05; ** 0.01; *** 0.001. To assess the consequences of reduced IFN-I production in mice, the levels of transcription of the IFN-inducible gene (interferon regulatory factor f) were measured by.