Reciprocal stimulation of gammadelta T cells and dendritic cells during the anti-mycobacterial immune response

γδ T cells and dendritic cells (DC) are two distinct cell types of innate immunity that participate in early phases of immune response against Mycobacterium tuberculosis infection. Here we show that a close functional relationship exists between these cell populations. Using an in vitro coculture system, Vγ1 T cells from Tcrb–/– mice were found to be activated by DC infected in vitro with BCG, as indicated by the elevated CD69 expression, IFN-γ secretion and cytotoxic activity. This activation process was due to a non-cognate mechanism since it required neither cell to cell contact nor interaction between the TCR and a specific antigen, but was mediated by DC-derived IL-12. Reciprocally, Vγ1 T cells provided a key cytokine, IFN-γ, which increased IL-12 production by BCG-infected DC. Moreover, exposure of BCG-infected DC to Vγ1 T cells conditioned the former to prime a significantly stronger anti-mycobacterial CD8 T cell response. Consequently, stimulation of γδ T cells and their non-cognate interaction with DC could be applied as an immune adjuvant strategy to optimize vaccine-induced CD8 T cell immunity.