Université Montpellier 1, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS) Montpellier, France.
PLoS One. 2012;7(8):e43613. doi: 10.1371/journal.pone.0043613. Epub 2012 Aug 22.
Vγ9Vδ2 T cells play an important role in the immune response to infectious agents but the mechanisms contributing to this immune process remain to be better characterized. Following their activation, Vγ9Vδ2 T cells develop cytotoxic activity against infected cells, secrete large amounts of cytokines and influence the function of other effectors of immunity, notably cells playing a key role in the initiation of the adaptive immune response such as dendritic cells. Brucella infection dramatically impairs dendritic cell maturation and their capacity to present antigens to T cells. Herein, we investigated whether V T cells have the ability to restore the full functional capacities of Brucella-infected dendritic cells. Using an in vitro multicellular infection model, we showed that: 1/Brucella-infected dendritic cells activate Vγ9Vδ2 T cells through contact-dependent mechanisms, 2/activated Vγ9Vδ2 T cells induce full differentiation into IL-12 producing cells of Brucella-infected dendritic cells with functional antigen presentation activity. Furthermore, phosphoantigen-activated Vγ9Vδ2 T cells also play a role in triggering the maturation process of dendritic cells already infected for 24 h. This suggests that activated Vγ9Vδ2 T cells could be used to modulate the outcome of infectious diseases by promoting an adjuvant effect in dendritic cell-based cellular therapies.
γ9δ2 T 细胞在针对感染因子的免疫反应中发挥重要作用，但有助于该免疫过程的机制仍有待更好地描述。γ9δ2 T 细胞活化后，对受感染的细胞产生细胞毒性作用，分泌大量细胞因子，并影响其他免疫效应物的功能，特别是在启动适应性免疫反应中起关键作用的细胞，如树突状细胞。布鲁氏菌感染会严重损害树突状细胞的成熟及其向 T 细胞呈递抗原的能力。在此，我们研究了 Vγ9δ2 T 细胞是否具有恢复布鲁氏菌感染的树突状细胞完全功能能力。使用体外多细胞感染模型，我们表明：1. 布鲁氏菌感染的树突状细胞通过接触依赖性机制激活 γ9δ2 T 细胞；2. 活化的 γ9δ2 T 细胞诱导布鲁氏菌感染的树突状细胞完全分化为产生 IL-12 的细胞，并具有功能性抗原呈递活性。此外，磷酸抗原激活的 γ9δ2 T 细胞还在触发已感染 24 小时的树突状细胞的成熟过程中发挥作用。这表明，活化的 γ9δ2 T 细胞可通过促进基于树突状细胞的细胞治疗中的佐剂效应，用于调节传染病的结局。
