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Administration of anti-CD25 mAb leads to impaired alpha-galactosylceramide-mediated induction of IFN-gamma production in a murine model
- Source :
- Rosalia, R A, Stepanek, I, Pollakova, V, Simova, J, Bieblova, J, Indrova, M, Moravcova, S, Pribylova, H, Bontkes, H J, Bubenik, J, Sparwasser, T & Reinis, M 2013, ' Administration of anti-CD25 mAb leads to impaired alpha-galactosylceramide-mediated induction of IFN-gamma production in a murine model ', Immunobiology, vol. 218, no. 6, pp. 851-859 . https://doi.org/10.1016/j.imbio.2012.10.012, Immunobiology, 218(6), 851-859. Urban und Fischer Verlag GmbH und Co. KG
- Publication Year :
- 2013
-
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.
- Subjects :
- Male
Regulatory T cell
medicine.medical_treatment
Immunology
Gene Expression
Enzyme-Linked Immunosorbent Assay
Galactosylceramides
Mice, Transgenic
chemical and pharmacologic phenomena
Kaplan-Meier Estimate
Biology
T-Lymphocytes, Regulatory
Interferon-gamma
Mice
Cancer immunotherapy
Cell Line, Tumor
Antineoplastic Combined Chemotherapy Protocols
medicine
Animals
Immunology and Allergy
Interferon gamma
IL-2 receptor
Interleukin 4
Reverse Transcriptase Polymerase Chain Reaction
Interleukin-2 Receptor alpha Subunit
Antibodies, Monoclonal
FOXP3
Forkhead Transcription Factors
hemic and immune systems
Neoplasms, Experimental
Hematology
Immunotherapy
Flow Cytometry
Natural killer T cell
Tumor Burden
Cell biology
Mice, Inbred C57BL
medicine.anatomical_structure
Intercellular Signaling Peptides and Proteins
Natural Killer T-Cells
Interleukin-4
Antigens, CD1d
Heparin-binding EGF-like Growth Factor
medicine.drug
Subjects
Details
- ISSN :
- 01712985
- Volume :
- 218
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Immunobiology
- Accession number :
- edsair.doi.dedup.....51acac0773816c4fad8252bca5ab24c4