Differential regulation of CD8+CD86+ Vγ1.1+ γδT cell responses in skin barrier tissue protection and homeostatic maintenance

Compared to αβT cells, γδT cells are more innate-like and preferentially function as the first line of defense in barrier tissues. Certain populations of γδT cells possess adaptive immune cell properties but their regulation is not well understood. We herein report that while innate-like γδT17 cells dominated in the skin of WT mice, Vγ1.1+ γδT cells with adaptive T cell-like properties predominantly expanded in the skin of TCRβ–/– and B2m–/– mice. Commensal bacteria drove expansion of Vγ1.1+ skin γδT cells, functional properties of which correlated with local immune requirements. That is, Vγ1.1+ skin γδT cells in TCRβ–/– mice were a heterogeneous population; while Vγ1.1+ skin γδT cells in B2m–/– mice were mostly CD8+CD86+ cells that had a similar function of CD8+CD86+ skin αβT cells in supporting local Treg cells. We also found that intrinsic TGF-β receptor 2-derived signals in skin CD8+ αβT and γδT cells are required for their expression of CD86, a molecule important in supporting skin Treg cells. Our findings reveal broad functional potentials of γδT cells that are coordinately regulated with αβT cells to help maintain local tissue homeostasis. © 2022 Wiley-VCH GmbH.