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Activated iNKT cells promote Vγ9Vδ2-T cell anti-tumor effector functions through the production of TNF-α
- Source :
-
Clinical Immunology . Feb2012, Vol. 142 Issue 2, p194-200. 7p. - Publication Year :
- 2012
-
Abstract
- Abstract: 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. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 15216616
- Volume :
- 142
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Clinical Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 71514509
- Full Text :
- https://doi.org/10.1016/j.clim.2011.10.006