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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.

proceedings of the national academy of sciences of the united states of america

Release of dendritic cells from cognate CD4 <sup>+</sup> T-cell recognition results in impaired peripheral tolerance and fatal cytotoxic T-cell mediated autoimmunity

Release of dendritic cells from cognate CD4 + T-cell recognition results in impaired peripheral tolerance and fatal cytotoxic T-cell mediated autoimmunity

Release of dendritic cells from cognate CD4 ⁺ T-cell recognition results in impaired peripheral tolerance and fatal cytotoxic T-cell mediated autoimmunity