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* Department of Internal Medicine I, University of Ulm, Ulm, Germany; and
Helmholtz Centre of Infection Research, Braunschweig, Germany
We investigated the negative effect of type I IFN (IFN-I) on the priming of specific CD8 T cell immunity. Priming of murine CD8 T cells is down-modulated if Ag is codelivered with IFN-I-inducing polyinosinic:polycytidylic acid (pI/C) that induces (NK cell- and T/B cell-independent) acute changes in the composition and surface phenotype of dendritic cells (DC). In wild-type but not IFN-I receptor-deficient mice, pI/C reduces the plasmacytoid DC but expands the CD8+ conventional DC (cDC) population and up-regulates surface expression of activation-associated (CD69, BST2), MHC (class I/II), costimulator (CD40, CD80/CD86), and coinhibitor (PD-L1/L2) molecules by cDC. Naive T cells are efficiently primed in vitro by IFN-I-stimulated CD8 cDC (the key APC involved in CD8 T cell priming) although these DC produced less IL-12 p40 and IL-6. pI/C (IFN-I)-mediated down modulation of CD8 T cell priming in vivo was not observed in NKT cell-deficient CD1d–/– mice. CD8 cDC from pI/C-treated mice inefficiently stimulated IFN-
, IL-4, and IL-2 responses of NKT cells. In vitro, CD8 cDC that had activated NKT cells in the presence of IFN-I primed CD8 T cells that produced less IFN- but more IL-10. The described immunosuppressive effect of IFN-I thus involves an NKT cell-mediated change in the phenotype of CD8 cDC that favors priming of IL-10-producing CD8 T cells. In the presence of IFN-I, NKT cells hence impair the competence of CD8 cDC to prime proinflammatory CD8 T cell responses.
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1 This work was supported by Grant Re549/10-3 from the Deutsche Forschungs-gemeinschaft (to J.R.).
2 Address correspondence and reprint requests to Dr. Joerg Reimann, Department of Internal Medicine I, University of Ulm, Albert Einstein Allee 11, Ulm, Germany. E-mail address: joerg.reimann{at}uni-ulm.de
3 Abbreviations used in this paper: DC, dendritic cell; cDC, conventional DC; DN, CD4– CD8– double negative; pDC, plasmacytoid DC; IFN-I, type I IFN; IFNAR, IFN-I receptor; wt, wild-type; pI/C, polyinosinic:polycytidylic acid; MCMV, murine cytomegalovirus; w/v, weight to volume ratio; FCM, flow cytometry; 
GalCer, -galactosyl-ceramide; NF, nonfractionated; BST2, bone marrow stroma cell antigen-2.
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