Administration of anti-CD25 mAb leads to impaired alpha-galactosylceramide-mediated induction of IFN-gamma production in a murine model

作者：Rosalia Rodney A; Stepanek Ivan; Pollakova Veronika; Simova Jana; Bieblova Jana; Indrova Marie; Moravcova Simona; Pribylova Hana; Bontkes Hetty J; Bubenik Jan; Sparwasser Tim; Reinis Milan^*

来源：Immunobiology, 2013, 218(6): 851-859.

DOI：10.1016/j.imbio.2012.10.012

• Cancer immunotherapy
• DEREG mice
• Interferon gamma
• Natural killer T cells
• PC61 monoclonal antibody
• T regulatory cells

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 %26quot;depletion of regulatory T cell%26quot; (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.

• 出版日期2013-6