Dermal Vγ4⁺ γδ T Cells Possess a Migratory Potency to the Draining Lymph Nodes and Modulate CD8⁺ T-Cell Activity through TNF-α Production

A large number of gamma delta T cells (γδ T cells) are located within epithelial tissues including the skin. In mice, epidermal and dermal γδ T cells consist of distinct subsets and have specific roles in cutaneous immune responses. A recent study demonstrated that γδ T cells and cutaneous dendritic cells migrate from the skin to the draining lymph nodes (LNs). However, it remains unclear whether they regulate the antigen-specific immune response within the LNs. Herein, we investigated their properties and role in the LNs using the Mycobacterium bovis bacille Calmette-Guérin (BCG) infection model. In vivo cell labeling analysis revealed that most of the migratory subset comprised dermal Vγ4⁺ cells. This population transmigrated from the skin to the LNs in a Gi-coupled chemokine receptor-independent manner. By depleting Vγ4⁺ cells, the intranodal expansion of CD8⁺ T cell against BCG was significantly attenuated. In addition, in vitro analysis revealed that Vγ4⁺ cells produced TNF- and enhanced IL-12 production by dendritic cells. Taken together, these findings suggest that dermal Vγ4⁺ cells are a unique subset that possesses a migratory potency to the skin-draining LNs and enhances the dendritic cell function therein.