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CD4^– Plasmacytoid Dendritic Cells (pDCs) Migrate in Lymph Nodes by CpG Inoculation and Represent a Potent Functional Subset of pDCs

Guo-Xiang Yang^1,*, Zhe-Xiong Lian^1,*, Kentaro Kikuchi^*, Yong-Jun Liu, Aftab A. Ansari, Susumu Ikehara and M. Eric Gershwin^2,*

^* Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA 95616; Department of Immunology, M. D. Anderson Cancer Center, Houston, TX 77030; Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322; and First Department of Pathology, Kansai Medical University, Osaka, Japan

We have recently identified two groups of plasmacytoid dendritic cells (pDCs) isolated from murine liver based on the expression of CD4 and other cell surface markers uniquely expressed by pDCs. Herein, we describe the identification of both CD4⁺ and CD4^– pDCs that clearly exist in lymph nodes (LNs), spleen, liver, thymus, bone marrow, and lung. Normally, CD4⁺ pDCs are enriched in LNs. However, after in vivo systemic injection with bacterial CpG, a larger number of CD4^– pDCs are recruited to the LNs and local inoculation by CpG drives CD4^– pDCs migrating into local sentinel LNs, suggesting that CD4^– pDCs are the main subpopulation migrating to the peripheral LNs. Furthermore, although both freshly isolated CD4⁺ pDCs and CD4^– pDCs appear as an immature plasmacytoid cell and develop into a DC morphology following activation, the two subsets have strikingly different immune features, including differences in the production pattern of cytokines stimulated with CpG and in T cell activation.

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