6533b870fe1ef96bd12d0559
RESEARCH PRODUCT
Release of dendritic cells from cognate CD4 + T-cell recognition results in impaired peripheral tolerance and fatal cytotoxic T-cell mediated autoimmunity
Hansjörg SchildSabine MuthKristian SchützeHans Christian Probstsubject
TransgeneGenes MHC Class IIAutoimmunityMice Transgenicchemical and pharmacologic phenomenaAdaptive ImmunityLymphocyte Activationmedicine.disease_causeT-Lymphocytes RegulatoryAutoimmunityMicemedicineAnimalsCytotoxic T cellHomeodomain ProteinsMHC class IIMultidisciplinarybiologyPeripheral ToleranceBody WeightHistological TechniquesFOXP3Peripheral tolerancehemic and immune systemsDendritic CellsBiological SciencesFlow CytometryAcquired immune systemTamoxifenImmunologybiology.proteinCD8T-Lymphocytes Cytotoxicdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-05-21 | Proceedings of the National Academy of Sciences |