期刊
CLINICAL IMMUNOLOGY
卷 162, 期 -, 页码 91-99出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2015.11.011
关键词
Tolerogenic dendritic cells; Cytokines; Regulatory T cells; Micro array; Suppression; T helper cell plasticity
类别
资金
- Sanquin PPOC grant [PPOC06-026]
Induced regulatory T cells (iTreg) are imperative for tolerance induction and spreading of infectious tolerance. Ex vivo generated tolerogenic dendritic cells (tDCs) have strong therapeutic potential to induce antigen-specific iTreg. We previously demonstrated that IL-10 tDC-primed T cells are very suppressive and produce IL-10. Here, we show that the majority of IL-10(+) T cells co-express IFN gamma, giving rise to the question whether these cells are proinflammatory or regulatory. Whole genome gene expression analysis revealed a strong regulatory gene profile and a suppressed Th1 gene profile for IL-10/IFN gamma co-expressing CD4(+) T cells. Protein analysis confirmed an extensive regulatory phenotype for IL-10(+)/IFN gamma(+) T cells, with specific enhanced expression of GARP and PD-1. In line with these data, isolated IL-10(+)/IFN gamma(+) T cells displayed potent suppressive capacity. Thus, IL-10/IFN gamma co-expressing CD4(+) T cells induced by IL-10 tDC show dominance of immunomodulation over Th1-mediated immunoactivation and can contribute to induction or spreading of immunological tolerance. (C) 2015 Elsevier Inc. All rights reserved.
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