Differential Regulation of CD8+ CD86+ Vγ1.1+ Γδt Cell Responses in Skin Barrier Tissue Protection and Homeostatic Maintenance.

Compared to alpha beta T cells, gamma delta T cells are more innate-like and preferentially function as the first line of defense in barrier tissues. Certain populations of gamma delta T cells possess adaptive immune cell properties but their regulation is not well understood. We herein report that while innate-like gamma delta T17 cells dominated in the skin of WT mice, V gamma 1.1(+) gamma delta T cells with adaptive T cell-like properties predominantly expanded in the skin of TCR beta(-/-) and B2m(-/-) mice. Commensal bacteria drove expansion of V gamma 1.1(+) skin gamma delta T cells, functional properties of which correlated with local immune requirements. That is, V gamma 1.1(+) skin gamma delta T cells in TCR beta(-/-) mice were a heterogeneous population; while V gamma 1.1(+) skin gamma delta T cells in B2m(-/-) mice were mostly CD8(+)CD86(+) cells that had a similar function of CD8(+)CD86(+) skin alpha beta T cells in supporting local Treg cells. We also found that intrinsic TGF-beta receptor 2-derived signals in skin CD8(+) alpha beta T and gamma delta T cells are required for their expression of CD86, a molecule important in supporting skin Treg cells. Our findings reveal broad functional potentials of gamma delta T cells that are coordinately regulated with alpha beta T cells to help maintain local tissue homeostasis.