Cutting Edge: Skin CCR10+ CD8+ T Cells Support Resident Regulatory T Cells through the B7.2/Receptor Axis To Regulate Local Immune Homeostasis and Response

Resident T cells in barrier tissues are important in protecting against foreign agents but can also contribute to inflammatory diseases if dysregulated. How T cell homeostasis is maintained in barrier tissues is still poorly understood. We report that resident CD8(+) T cells directly support maintenance of regulatory T cells (Tregs) in the skin to promote immune homeostasis. Impaired establishment of resident CD8(+) T cells caused by knockout of the skin-homing chemokine receptor CCR10 resulted in an altered balance of resident Tregs and CD4(+) effector T cells in the skin and overreactive inflammatory responses to cutaneous stimulations. Furthermore, B7.2 expressed on skin CD8(+) T cells supports the survival of Tregs, likely through interaction with its receptor CTLA-4, which is highly expressed on skin Tregs. Our findings provide novel insights into T cell homeostatic regulation in the skin and may improve our understanding of the pathobiology of tissue inflammatory diseases.