Activated iNKT cells promote Vγ9Vδ2-T cell anti-tumor effector functions through the production of TNF-α
Copyright © 2011 Elsevier Inc. All rights reserved.
Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 142(2012), 2 vom: 11. Feb., Seite 194-200 |
---|---|
1. Verfasser: | |
Weitere Verfasser: | , , , , , , , |
Format: | Online-Aufsatz |
Sprache: | English |
Veröffentlicht: |
2012
|
Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Antigens, Neoplasm Diphosphonates Galactosylceramides Hemiterpenes Immunologic Factors Organophosphorus Compounds Tumor Necrosis Factor-alpha alpha-galactosylceramide mehr... |
Zusammenfassung: | Copyright © 2011 Elsevier Inc. All rights reserved. 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 |
---|---|
Beschreibung: | Date Completed 11.04.2012 Date Revised 06.02.2012 published: Print-Electronic Citation Status MEDLINE |
ISSN: | 1521-7035 |
DOI: | 10.1016/j.clim.2011.10.006 |