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.
- MeSH
- antigeny CD1d imunologie metabolismus MeSH
- ELISA MeSH
- experimentální nádory farmakoterapie imunologie patologie MeSH
- exprese genu účinky léků imunologie MeSH
- forkhead transkripční faktory imunologie metabolismus MeSH
- galaktosylceramidy aplikace a dávkování imunologie farmakologie MeSH
- interferon gama genetika imunologie metabolismus MeSH
- interleukin-4 genetika imunologie metabolismus MeSH
- Kaplanův-Meierův odhad MeSH
- mezibuněčné signální peptidy a proteiny genetika imunologie metabolismus MeSH
- monoklonální protilátky aplikace a dávkování imunologie farmakologie MeSH
- myši inbrední C57BL MeSH
- myši transgenní MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- NKT buňky účinky léků imunologie metabolismus MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- průtoková cytometrie MeSH
- receptor interleukinu-2 - alfa-podjednotka imunologie metabolismus MeSH
- regulační T-lymfocyty účinky léků imunologie metabolismus MeSH
- tumor burden účinky léků imunologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
