title: Administration of anti-CD25 mAb leads to impaired α-galactosylceramide-mediated induction of IFN-γ production in a murine model.
abstract: 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, α-galactosylceramide (α-GalCer)-mediated activation of iNKT cells resulted in decreased IFN-γ but not IL-4 production. In order to determine whether mutual interactions between Tregs and iNKT cells take place, we compared IFNγ production after α-GalCer administration in anti-CD25-treated and "depletion of regulatory T cell" (DEREG) mice. Since no profound effects on IFNγ 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 α-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.
authors.affiliation: Department of Tumour Immunology of the Institute of Molecular Genetics, v. v. i., Academy of Sciences of the Czech Republic, Prague 4, Czech Republic.
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Rosalia
authors.forename: Ivan
authors.initials: I
authors.lastname: Štěpánek
authors.forename: Veronika
authors.initials: V
authors.lastname: Polláková
authors.forename: Jana
authors.initials: J
authors.lastname: Šímová
authors.forename: Jana
authors.initials: J
authors.lastname: Bieblová
authors.forename: Marie
authors.initials: M
authors.lastname: Indrová
authors.forename: Simona
authors.initials: S
authors.lastname: Moravcová
authors.forename: Hana
authors.initials: H
authors.lastname: Přibylová
authors.forename: Hetty J
authors.initials: HJ
authors.lastname: Bontkes
authors.forename: Jan
authors.initials: J
authors.lastname: Bubeník
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.forename: Milan
authors.initials: M
authors.lastname: Reiniš
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D055610:Antigens, CD1d / Q000276:immunology / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D005699:Galactosylceramides / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology* / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D055610:Antigens, CD1d; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D005699:Galactosylceramides; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D053645:Interleukin-2 Receptor alpha Subunit; C584092:PC61 monoclonal antibody; C493154:alpha-galactosylceramide; D015847:Interleukin-4; D007371:Interferon-gamma