| Autor: |
Maksimow M; MediCity Research Laboratory, University of Turku, Tykistökatu 6A, 20520 Turku, Finland., Miiluniemi M, Marttila-Ichihara F, Jalkanen S, Hänninen A |
| Jazyk: |
angličtina |
| Zdroj: |
Blood [Blood] 2006 Aug 15; Vol. 108 (4), pp. 1298-305. Date of Electronic Publication: 2006 Apr 18. |
| DOI: |
10.1182/blood-2005-11-008615 |
| Abstrakt: |
Lymphoma cells are malignant cells of the T- or B-cell lineage that often express many surface markers inappropriately, yet are not recognized as abnormal by the immune system. We modeled this situation by inoculating ovalbumin-expressing E.G7-OVA lymphoma cells into mice that expressed ovalbumin as a self antigen in pancreatic islets, and investigated the efficacy of dendritic cell (DC) vaccination in these mice. Although vaccination with DC-expressing ovalbumin induced strong cytotoxic T-cell immunity, which led to clearance of E.G7-OVA lymphoma cells in naive C57BL/6 mice, DC vaccination was ineffective in mice expressing ovalbumin as a self antigen. Antigen modification to increase its processing via the endosomal processing pathway dramatically increased CD4 T-cell activation but paradoxically, impaired the protective effect of DC vaccination even in naive mice. Depletion of CD25(+) T cells (regulatory T cells [Tregs]) prior to vaccination restored the efficacy of DC vaccination and allowed eradication of lymphoma also in mice expressing ovalbumin as a self antigen. We conclude that lymphoma cells may be eradicated using DC vaccination if activation of CD25(+) Tregs is simultaneously inhibited, and that intentionally enhanced endosomal antigen processing in DC vaccines may shift the balance from CD4 T-cell help toward stimulation of Tregs. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
