Simultaneous Induction of CD4 T Cell Tolerance and CD8 T Cell Immunity by Semimature Dendritic Cells

Previous studies suggested that depending on their maturation state, dendritic cells (DC) could either induce T cell tolerance (immature and semimature DC) or T cell activation (mature DC). Pretreatment of C57BL/6 mice with encephalitogenic myelin oligodendrocyte glycoprotein (MOG)(35-55) peptide-lo...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2005-04, Vol.174 (7), p.3941-3947
Main Authors: Kleindienst, Petra, Wiethe, Carsten, Lutz, Manfred B, Brocker, Thomas
Format: Article
Language:English
Subjects:
Animals
Antigen Presentation
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
Cytotoxicity, Immunologic
Dendritic Cells - immunology
Dendritic Cells - physiology
Diabetes Mellitus, Experimental - immunology
Encephalomyelitis, Autoimmune, Experimental - immunology
Glycoproteins - immunology
Immune Tolerance
Immunity, Cellular
Lymphocyte Activation - immunology
Mice
Mice, Inbred C57BL
Myelin-Oligodendrocyte Glycoprotein
Ovalbumin - immunology
Peptide Fragments - immunology
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Summary:Previous studies suggested that depending on their maturation state, dendritic cells (DC) could either induce T cell tolerance (immature and semimature DC) or T cell activation (mature DC). Pretreatment of C57BL/6 mice with encephalitogenic myelin oligodendrocyte glycoprotein (MOG)(35-55) peptide-loaded semimature DC protected from MOG-induced autoimmune encephalomyelitis. This protection was mediated by IL-10-producing CD4 T cells specific for the self Ag. Here we show that semimature DC loaded with the MHC class II-restricted nonself peptide Ag (OVA) induce an identical regulatory T cell cytokine pattern. However, semimature DC loaded simultaneously with MHC class II- and MHC class I-restricted peptides, could efficiently initiate CD8 T cell responses leading to autoimmune diabetes in a TCR-transgenic adoptive transfer model. Double-peptide-loaded semimature DC also induced simultaneously in the same animal partially activated CD8 T cells with cytolytic function as well as protection from MOG-induced autoimmune encephalomyelitis. Our study suggests that the decision between tolerance and immunity not only depends on the DC, but also on the type and activation requirements of the responding T cell.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.174.7.3941