Interaction with activated monocytes enhances cytokine expression and suppressive activity of human CD4+CD45RO+CD25+CD127low regulatory T cells
Journal of Translational Medicine volume 10, Article number: P3 (2012)
Despite the high frequency of CD4+ T cells with a regulatory phenotype (CD25+CD127lowFoxP3+) in the joints of patients with rheumatoid arthritis (RA), inflammation persists. Regulatory T cells (Tregs) can be converted into pro-inflammatory IL-17-producing cells by inflammatory mediators, particularly IL-1β.
To investigate whether activated monocytes, which are abundantly present in the rheumatic joint and potent producers of IL-1β, induce pro-inflammatory cytokine expression in Tregs and whether this impairs Treg function.
Materials and methods
The presence and phenotype of CD4+CD45RO+CD25+CD127low T cells (memory Tregs) and CD14+ monocytes in the peripheral blood (PB) and synovial fluid (SF) from patients with RA was investigated by flow cytometry. FACS-sorted memory Tregs from healthy controls were co-cultured with autologous in vitro-activated monocytes and anti-CD3 monoclonal antibody. Intracellular cytokine expression, phenotype and function were determined by flow cytometry, ELISA and proliferation assays.
Patients with RA showed higher frequencies of CD4+CD45RO+CD25+CD127low Tregs and activated CD14+ monocytes in SF relative to PB. We demonstrate that activated monocytes induced an increase in the percentage of IL-17+, IFNγ+ and TNF-α+, but also IL-10+ Tregs. Blocking and reconstitution experiments revealed that the observed increase in IL-17+ and IFNγ+ Tregs was driven by monocyte-derived IL-1β, IL-6 and TNF-α and was mediated by both CD14+CD16- and CD14+CD16+ monocyte subsets. Despite enhanced cytokine expression, cells maintained their CD25+FoxP3+CD39+ Treg phenotype and showed enhanced capacity to suppress proliferation and IL-17 production by effector T cells.
Tregs exposed to a pro-inflammatory environment show increased suppressive activity.
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Walter, G.J., Evans, H.G., Menon, B. et al. Interaction with activated monocytes enhances cytokine expression and suppressive activity of human CD4+CD45RO+CD25+CD127low regulatory T cells. J Transl Med 10 (Suppl 3), P3 (2012). https://doi.org/10.1186/1479-5876-10-S3-P3