The Journal of Immunology Plasticity of Ly-6Chi Myeloid Cells in T Cell Regulation

CD11b+Ly-6Chi cells, including inflammatory monocytes (IMCs) and inflammatory dendritic cells (IDCs), are important in in-fectious, 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-g, GM-CSF, TNF-a, and CD154 derived from activated T cells during their interaction. In experi-mental 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. The Journal of Immunology, 2011, 187: 2418–2432. M ononuclear leukocytes, including monocytes, macro-phages, and dendritic cells, play essential roles in shaping the T cell response (1, 2). They sense dange