1A and B) Of note, although at low frequencies, IFNAR−/− P14 cel

1A and B). Of note, although at low frequencies, IFNAR−/− P14 cells were still detectable at day 37 post-infection in the blood, indicating that memory T cells developed and were maintained over a long time period, as also observed for single LCMV infection 19. This finding

could be confirmed by monitoring the total number of IFNAR−/− P14 www.selleckchem.com/products/Gefitinib.html cells in spleen and LNs 45 days post-infection (Figs. 1B and 6). For further functional analyses we focused on day 3 and day 6 post-infection, as at these time points the numbers of IFNAR−/− P14 cells were sufficient for detailed analysis. To determine whether impaired expansion of IFNAR−/− P14 cells was accompanied by altered effector functions, we measured click here their capacity to secrete IFN-γ upon in vitro peptide restimulation. In accordance with our recent studies 17, we found that cells lacking type-I IFN signaling showed less capacity to secrete IFN-γ as well as to degranulate (measured by cell surface CD107a mobilization) compared with WT P14 cells (Fig. 1C and D) while expressing comparable levels of perforin and granzyme B (Fig.

1D). Thus, although IFNAR−/− CD8+ T cells initially expanded and gained effector functions, albeit at reduced levels, type-I IFN signaling was a major promoter of their expansion, survival and effector differentiation under inflammatory conditions

of an LCMV infection. It is well established that type-I IFN and IL-12 have redundant functions in their role as a third signal during CD8+ T-cell activation; both pro-inflammatory cytokines can promote expansion as well as survival of activated CD8+ T cells in vivo 13, 18–20. Additionally, there is abundant evidence that IL-12 signaling during CD8+ T-cell priming promotes the terminal differentiation of short-lived effector cells 3–5. However, a direct role of type-I IFN in SLEC formation in vivo has not been Dichloromethane dehalogenase studied to date. Thus, we examined in vivo the expression of cell surface markers which have been described to identify SLECs (CD44high, CD127low, KLRG1high) and MPECs (CD44high, CD127high, KLRG1low) 3 and 6 days post co-infection. Notably, WT and IFNAR−/− P14 cells showed comparable naïve phenotypes (CD44low, CD25low, CD127high, KLRG1low and CD62Lhigh) (Fig. 2A and data not shown). WT P14 cells exhibited a pronounced upregulation of CD25 as early as day 3 post-infection (Fig. 2A and B), whereas IFNAR−/− P14 cells in the same recipients only slightly increased CD25 expression. By day 3 post-infection, WT P14 cells could be divided into two populations with respect to CD62L expression (CD62Lhigh and CD62Llow) and by day 6 the majority of the WT P14 cells showed low expression of CD62L.

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