γ δ T Cells and Dendritic Cells: Close Partners and Biological Adjuvants for New Therapies

The knowledge of several signals influencing Dendritic Cell (DC) functions is crucial to manipulate the immune system for new vaccination therapies. Our recent findings provide a new model of intervention on DC system suggesting novel therapeutic implications. T, NK, and γ δ T cell stimuli may enhance DC maturation, Th polarization and trigger the adaptive immune response. Regulatory effects of γ δ T cells on inflammation and immune responses may be mediated by their interaction with DCs and they are analyzed in the last years in humans and mice. In humans, Vγ9Vδ2 T cells represent the most part of circulating γ δ T cells and are activated by non-peptidic molecules derived from different microorganisms or abnormal metabolic routes. They share both NK-like and effector/memory T cell features, and among these the possibility to interact with DCs. Coculture of immature DCs with activated Vγ9Vδ2 T cells allows DCs to acquire features of mature DCs complementing the migratory activity, up-regulating the chemokine receptors, and antigen presentation. Similarly to the NK-derived signals, DC activation is mostly mediated by soluble factors secreted by γ δ T cells. Many non-peptidic molecules including nitrogen-containing bisphosphonates and pyrophosphomonoester drugs stimulate the activity of Vγ9Vδ2 T cells in vitro and in vivo. The relatively low in vivo toxicity of many of these drugs makes possible novel vaccine and immune-based strategies, through DCs, for infectious and neoplastic diseases.