title: Plasticity of Ly-6C(hi) myeloid cells in T cell regulation.
abstract: CD11b(+)Ly-6C(hi) 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. Nonactivated 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-6C(hi) 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-6C(hi) 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-6C(hi) myeloid cells, which in turn suppress T cells and lead to the contraction of local immune response.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhu
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Kennedy
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Carolina
authors.initials: C
authors.lastname: Sandoval-Garcia
authors.forename: Li
authors.initials: L
authors.lastname: Cao
authors.forename: Sheng
authors.initials: S
authors.lastname: Xiao
authors.forename: Chuan
authors.initials: C
authors.lastname: Wu
authors.forename: Wassim
authors.initials: W
authors.lastname: Elyaman
authors.forename: Samia J
authors.initials: SJ
authors.lastname: Khoury
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000950:Antigens, Ly / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology*; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D000950:Antigens, Ly; C494192:Ly-6C antigen, mouse