Plasticity of Ly-6Chi myeloid cells in T cell regulation

Bing Zhu, Jennifer K. Kennedy, Yue Wang, Carolina Sandoval-Garcia, Li Cao, Sheng Xiao, Chuan Wu, Wassim Elyaman, Samia J. Khoury

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

CD11b+Ly-6Chi cells, including inflammatory monocytes (IMCs) and inflammatory dendritic cells (IDCs), are important in infectious, autoimmune, and tumor models. However, their role in T cell regulation is controversial. In this article, we show that T cell regulation by IMCs and IDCs is determined by their activation state and is plastic during an immune response. Non-activated IMCs and IDCs function as APCs, but activated IMCs and IDCs suppress T cells through NO production. Suppressive IMCs are induced by IFN-γ, GM-CSF, TNF-α, and CD154 derived from activated T cells during their interaction. In experimental autoimmune encephalomyelitis, CD11b+Ly-6Chi cells in the CNS are increasingly activated from disease onset to peak and switch their function from Ag presentation to T cell suppression. Furthermore, transfer of activated IMCs or IDCs enhances T cell apoptosis in the CNS and suppresses experimental autoimmune encephalomyelitis. These data highlight the interplay between innate and adaptive immunity: immunization leads to the expansion of Ly-6Chi myeloid cells initially promoting T cell function. As T cells become highly activated in the target tissue, they induce activation and NO production in Ly-6Chi myeloid cells, which in turn suppress T cells and lead to the contraction of local immune response.

Original languageEnglish (US)
Pages (from-to)2418-2432
Number of pages15
JournalJournal of Immunology
Volume187
Issue number5
DOIs
StatePublished - Sep 1 2011
Externally publishedYes

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