title: Release of dendritic cells from cognate CD4+ T-cell recognition results in impaired peripheral tolerance and fatal cytotoxic T-cell mediated autoimmunity.
abstract: Resting dendritic cells (DCs) induce tolerance of peripheral T cells that have escaped thymic negative selection and thus contribute significantly to protection against autoimmunity. We recently showed that CD4(+)Foxp3(+) regulatory T cells (Tregs) are important for maintaining the steady-state phenotype of DCs and their tolerizing capacity in vivo. We now provide evidence that DC activation in the absence of Tregs is a direct consequence of missing DC-Treg interactions rather than being secondary to generalized autoimmunity in Treg-less mice. We show that DCs that lack MHC class II and thus cannot make cognate interactions with CD4(+) T cells are completely unable to induce peripheral CD8(+) T-cell tolerance. Consequently, mice in which interactions between DC and CD4(+) T cells are not possible develop spontaneous and fatal cytotoxic T lymphocyte-mediated autoimmunity.
authors.affiliation: Institute for Immunology,  University Medical Center of the Johannes Gutenberg University Mainz, D-55131 Mainz  Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Muth
authors.forename: Kristian
authors.initials: K
authors.lastname: Schütze
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Schild
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Probst
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D001835:Body Weight; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology; D006652:Histological Techniques; D018398:Homeodomain Proteins; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D061166:Peripheral Tolerance / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013629:Tamoxifen
chemical_list: D018398:Homeodomain Proteins; D013629:Tamoxifen; C064658:RAG-1 protein