Dermal V gamma 4(+) gamma delta T Cells Possess a Migratory Potency to the Draining Lymph Nodes and Modulate CD8(+) T-Cell Activity through TNF-alpha Production

A large number of gamma delta T cells (gamma delta T cells) are located within epithelial tissues including the skin. In mice, epidermal and dermal gamma delta T cells consist of distinct subsets and have specific roles in cutaneous immune responses. A recent study demonstrated that gamma delta 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-Guerin (BCG) infection model. In vivo cell labeling analysis, revealed that most of the migratory subset comprised dermal V gamma 4(+) cells. This population transmigrated from the skin to the LNs in a Gi-coupled chemokine receptor independent manner. By depleting V gamma 4(+) cells, the intranodal expansion of CD8(+) T cell against BCG was significantly attenuated. In addition, in vitro analysis revealed that V gamma 4(+) cells produced TNF-alpha and enhanced IL-12 production by dendritic cells. Taken together, these findings suggest that dermal V gamma 4(+) cells are a unique subset that possesses a migratory potency to the skin-draining LNs and enhances the dendritic cell function therein.