Sacchi Alessandra, Rinaldi Alessandra, Tumino Nicola, Casetti Rita, Agrati Chiara, Turchi Federica, Bordoni Veronica, Cimini Eleonora, Martini Federico
Laboratory of Cellular Immunology, National Institute for Infectious Diseases "Lazzaro Spallanzani", Rome, Italy.
Laboratory of Cellular Immunology, National Institute for Infectious Diseases "Lazzaro Spallanzani", Rome, Italy; Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
PLoS One. 2014 Oct 23;9(10):e111095. doi: 10.1371/journal.pone.0111095. eCollection 2014.
DCs act as sentinel cells against incoming pathogens and represent the most potent antigen presenting cells, having the unique capability to prime naïve T cells. In addition to their role in induction of adaptive immune responses, DC are also able to activate innate cells as γδ T cells; in particular, a reciprocal crosstalk between DC and γδ T cells was demonstrated. However, whether HIV infection may alter DC-Vγ9Vδ2 T cells cross-talk was not yet described. To clarify this issue, we cultured activated Vγ9Vδ2 T cells with HIV infected monocyte derived DC (MoDC). After 5 days we evaluated MoDC phenotype, and Vγ9Vδ2 T cells activation and proliferation. In our model, Vγ9Vδ2 T cells were not able to proliferate in response to HIV-infected MoDC, although an up-regulation of CD69 was observed. Upon phosphoantigens stimulation, Vγ9Vδ2 T cells proliferation and cytokine production were inhibited when cultured with HIV-infected MoDC in a cell-contact dependent way. Moreover, HIV-infected MoDC are not able to up-regulate CD86 molecules when cultured with activated Vγ9Vδ2 T cells, compared with uninfected MoDC. Further, activated Vγ9Vδ2 T cells are not able to induce HLA DR up-regulation and CCR5 down-regulation on HIV-infected MoDC. These data indicate that HIV-infected DC alter the capacity of Vγ9Vδ2 T cells to respond to their antigens, pointing out a new mechanisms of induction of Vγ9Vδ2 T cells anergy carried out by HIV, that could contribute to immune evasion.
树突状细胞（DCs）作为抵御外来病原体的哨兵细胞，是最强大的抗原呈递细胞，具有启动初始T细胞的独特能力。除了在诱导适应性免疫反应中的作用外，DC还能够激活先天细胞，如γδT细胞；特别是，已证明DC与γδT细胞之间存在相互串扰。然而，HIV感染是否会改变DC-Vγ9Vδ2 T细胞的串扰尚未见报道。为了阐明这个问题，我们将活化的Vγ9Vδ2 T细胞与HIV感染的单核细胞衍生DC（MoDC）一起培养。5天后，我们评估了MoDC的表型以及Vγ9Vδ2 T细胞的活化和增殖情况。在我们的模型中，Vγ9Vδ2 T细胞不能对HIV感染的MoDC做出增殖反应，尽管观察到CD69上调。在磷酸抗原刺激下，当与HIV感染的MoDC以细胞接触依赖的方式培养时，Vγ9Vδ2 T细胞的增殖和细胞因子产生受到抑制。此外，与未感染的MoDC相比，HIV感染的MoDC与活化的Vγ9Vδ2 T细胞一起培养时不能上调CD86分子。此外，活化的Vγ9Vδ2 T细胞不能诱导HIV感染的MoDC上的HLA DR上调和CCR5下调。这些数据表明，HIV感染的DC改变了Vγ9Vδ2 T细胞对抗原做出反应的能力，指出了HIV诱导Vγ9Vδ2 T细胞无反应性的一种新机制，这可能有助于免疫逃逸。
