کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6087771 | 1207398 | 2012 | 7 صفحه PDF | دانلود رایگان |

Vγ9Vδ2-T cells constitute a proinflammatory lymphocyte subpopulation with established antitumor activity. Phosphoantigens activate Vγ9Vδ2-T cells in vivo and in vitro. We studied whether the antitumor activity of Vγ9Vδ2-T cells can be potentiated by invariant NKT cells (iNKT), an important immunoregulatory T cell subset. When activated by the glycolipid α-galactosylceramide (α-GalCer), iNKT produce large amounts of cytokines involved in antitumor immune responses. Monocyte-derived dendritic cells were loaded with both phosphoantigens (using aminobisphosphonates) and α-GalCer during maturation and subsequently co-cultured with Vγ9Vδ2-T and iNKT cells. Aminobisphosphonates dose-dependently enhanced Vγ9Vδ2-T cell activation, and this was potentiated by α-GalCer-induced iNKT co-activation. iNKT co-activation also enhanced the IFN-γ production and cytolytic potential of Vγ9Vδ2-T cells against tumor cells. Using transwell experiments and neutralizing antibodies cross-talk between iNKT and Vγ9Vδ2-T cells was found to be mediated by TNF-α. Our data provide a rationale for combining both activating ligands to improve Vγ9Vδ2-T cell based approaches in cancer-immunotherapy.
⺠Vγ9Vδ2-T cells are proinflammatory lymphocytes with established antitumor activity ⺠Immunoregulatory iNKT cells initiate and propagate antitumor immune responses ⺠Activated iNKT enhance Vγ9Vδ2-T activation, cytokine production and cytotoxicity ⺠Stimulation of Vγ9Vδ2-T by iNKT is cell-contact independent and mediated by TNF-α ⺠There is rationale for studying iNKT co-activation in Vγ9Vδ2-T based immunotherapy
Journal: Clinical Immunology - Volume 142, Issue 2, February 2012, Pages 194-200