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Type I IFN-Induced, NKT Cell-Mediated Negative Control of CD8 T Cell Priming by Dendritic Cells

Content Provider	Scilit
Author	Bochtler, Petra Kröger, Andrea Schirmbeck, Reinhold Reimann, Jörg
Copyright Year	2008
Description	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-γ, 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-γ 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.
Ending Page	1643
Page Count	11
Starting Page	1633
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.181.3.1633
Journal	The Journal of Immunology
Issue Number	3
Volume Number	181
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2008-08-01
Access Restriction	Open
Subject Keyword	Cd8 T Cell Priming Nkt Cell Mediated Nkt Cells
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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