期刊
IMMUNOBIOLOGY
卷 218, 期 6, 页码 851-859出版社
ELSEVIER GMBH
DOI: 10.1016/j.imbio.2012.10.012
关键词
Cancer immunotherapy; DEREG mice; Interferon gamma; Natural killer T cells; PC61 monoclonal antibody; T regulatory cells
类别
资金
- Grant Agency of the Czech Republic [301/07/1410, 301/10/2174]
- Academy of Sciences of the Czech Republic [AV0Z50520514]
- Dutch Cancer Society
CD4(+)CD25(+)Foxp3(+) T regulatory cells (Tregs) and CD1d-restricted invariant natural killer T (iNKT) cells are two cell types that are known to regulate immune reactions. Depletion or inactivation of Tregs using specific anti-CD25 antibodies in combination with immunostimulation is an attractive modality especially in anti-tumour immunotherapy. However, CD25 is not expressed exclusively on Tregs but also on subpopulations of activated lymphocytes. Therefore, the modulatory effects of the specific anti-CD25 antibodies can also be partially attributed to their interactions with the effector cells. Here, the effector functions of iNKT cells were analysed in combination with anti-CD25 mAb PC61. Upon PC61 administration, alpha-galactosylceramide (alpha-GalCer)-mediated activation of iNKT cells resulted in decreased IFN-gamma but not IL-4 production. In order to determine whether mutual interactions between Tregs and iNKT cells take place, we compared IFN gamma production after alpha-GalCer administration in anti-CD25-treated and depletion of regulatory T cell (DEREG) mice. Since no profound effects on IFN gamma induction were observed in DEREG mice, deficient in FoxP3(+) Tregs, our results indicate that the anti-CD25 antibody acts directly on CD25(+) effector cells. In vivo experiments demonstrated that although both alpha-GalCer and PC61 administration inhibited TC-1 tumour growth in mice, no additive/synergic effects were observed when these substances were used in combination therapy. (C) 2012 Elsevier GmbH. All rights reserved.
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