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

0395907 - ÚMG 2014 RIV DE eng J - Journal Article
Rosalia, Rodney Alexander - Štěpánek, Ivan - Polláková, Veronika - Šímová, Jana - Bieblová, Jana - Indrová, Marie - Moravcová, Simona - Přibylová, Hana - Bontkes, H. - Bubeník, Jan - Sparwasser, T. - Reiniš, Milan
Administration of anti-CD25 mAb leads to impaired alpha-galactosylceramide-mediated induction of IFN-gamma production in a murine model.
Immunobiology. Roč. 218, č. 6 (2013), s. 851-859. ISSN 0171-2985
R&D Projects: GA ČR GA301/07/1410; GA ČR GAP301/10/2174
Institutional research plan: CEZ:AV0Z50520514
Institutional support: RVO:68378050
Keywords : cancer immunotherapy * DEREG mice * interferon γ * natural killer T cells * PC61 monoclonal antibody * T regulatory cells
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 3.180, year: 2013

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.
Permanent Link: http://hdl.handle.net/11104/0228410