Reciprocal stimulation of γδ T cells and dendritic cells during the anti‐mycobacterial immune response

Abstract

cd Tcells 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, Vc1 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-c 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, Vc1 T cells provided a key cytokine, IFN-c, which increased IL-12 production by BCG-infected DC. Moreover, exposure of BCGinfected DC to Vc1 T cells conditioned the former to prime a significantly stronger antimycobacterial CD8 T cell response. Consequently, stimulation of cd T cells and their noncognate interaction with DC could be applied as an immune adjuvant strategy to optimize vaccine-induced CD8 T cell immunity.

γδ T cells condition dendritic cells in vivo for priming pulmonary CD8 T cell responses against Mycobacterium tuberculosis

“…Our previous in vitro studies showed that cd T cells significantly influence the development of antigen-specific cytotoxic CD8 T cells, and this effect seems to be mediated by DC. These cellular interactions suggest that cd T cells might help to control mycobacterial infection in the transition period between innate and CD8 T cell-mediated adaptive immunity [17]. These in vitro studies have been expanded in this paper to in vivo conditions, using Tcrd -/-mice.…”

“…This non-cognate interaction conditions DC for effective priming of anti-mycobacterial CD8 T cell responses [17]. We therefore asked whether cd T cells influence the activity of lung DC in vivo.…”

“…Lung cd T cells provide an early source of IFN-c Upon in vitro activation, cd Tcells predominantly produce , which augments in vitro IL-12 production by BCG-infected DC [17]. Therefore, we hypothesized that cd T cells recruited to the lungs after BCG infection might influence DC, and consequently CD8 T cell activation, through IFN-c production.…”

“…with BCG, and they produce IFN-c following in vitro stimulation and are cytotoxic against BCG-infected macrophages [16]. Evidence from mouse [17] and human [18,19] studies suggests that cd T cells may participate in adaptive immune responses by modulating DC functions [14] or by producing . In mice, cd T cells are important in the generation of adaptive and protective responses in some infection models but are dispensable in others [21][22][23].…”

Current progress in γδ T-cell biology

“…are also involved in cd T-cell activation. 23,25,[51][52][53][54] Moens and colleagues showed that human neonatal DC-derived IL-23 combined with specific TCR signaling drives the generation of neonatal Vc9Vd2 T cells equipped with a range of cytotoxic mediators and distinct subpopulations producing IFN-c and IL-17. Dimova and colleagues revealed that the immune response after bacillus Calmette-Guérin vaccination of infants can drive cd T cells into an effector cell type that produce IFN-c and mediate cytotoxicity.…”