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CD83-stimulated monocytes suppress T-cell immune responses through production of prostaglandin E2

Chen, Liwen, Zhu, Yibei, Zhang, Guangbo, Gao, Chao, Zhong, Weixue, Zhang, Xueguang
Proceedings of the National Academy of Sciences of the United States of America 2011 v.108 no.46 pp. 18778-18783
CD4-positive T-lymphocytes, dendritic cells, immune response, interferon-gamma, monocytes, transforming growth factor beta
CD83 is commonly known as a specific marker for mature dendritic cells. It has been shown to be important for CD4+ T-cell development in the thymus. However, its function in the peripheral immune system remains enigmatic. Here, we show that CD83 inhibits proliferation and production of IL-2 and IFN-γ by T cells, and the inhibitory effect of CD83 is mediated by monocytes. Prostaglandin E2 (PGE2), but not IL-10 or TGF-β, was up-regulated specifically by CD83 in monocytes. Consistent with high levels of PGE2, expression of COX-2 also was increased upon CD83 treatment. NF-κB activation also is required for induction of PGE2 by CD83. Finally, application of the COX-2–selective inhibitor NS-398 fully prevented CD83-triggered inhibition of T-cell responses. Our study establishes an immune-regulatory mechanism by CD83 via stimulation of PGE2 production in monocytes.