TY - JOUR
T1 - Plasticity of Ly-6Chi myeloid cells in T cell regulation
AU - Zhu, Bing
AU - Kennedy, Jennifer K.
AU - Wang, Yue
AU - Sandoval-Garcia, Carolina
AU - Cao, Li
AU - Xiao, Sheng
AU - Wu, Chuan
AU - Elyaman, Wassim
AU - Khoury, Samia J.
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/9/1
Y1 - 2011/9/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1100403
DO - 10.4049/jimmunol.1100403
M3 - Article
C2 - 21824867
AN - SCOPUS:80052671020
SN - 0022-1767
VL - 187
SP - 2418
EP - 2432
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -