Plasmacytoid DCs help lymph node DCs to induce anti-HSV CTLs.
Antiviral cell-mediated immunity is initiated by the dendritic cell (DC) network in lymph nodes (LNs). Plasmacytoid DCs (pDCs) are known to migrate to inflamed LNs and produce interferon (IFN)-alpha, but their other roles in antiviral T cell immunity are unclear. We report that LN-recruited pDCs are activated to create local immune fields that generate antiviral cytotoxic T lymphocytes (CTLs) in association with LNDCs, in a model of cutaneous herpes simplex virus (HSV) infection. Although pDCs alone failed to induce CTLs, in vivo depletion of pDCs impaired CTL-mediated virus eradication. LNDCs from pDC-depleted mice showed impaired cluster formation with T cells and antigen presentation to prime CTLs. Transferring circulating pDC precursors from wild-type, but not CXCR3-deficient, mice to pDC-depleted mice restored CTL induction by impaired LNDCs. In vitro co-culture experiments revealed that pDCs provided help signals that recovered impaired LNDCs in a CD2- and CD40L-dependent manner. pDC-derived IFN-alpha further stimulated the recovered LNDCs to induce CTLs. Therefore, the help provided by pDCs for LNDCs in primary immune responses seems to be pivotal to optimally inducing anti-HSV CTLs.
Yoneyama
Hiroyuki
H
Department of Molecular Preventive Medicine and Solution Oriented Research for Science and Technology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Matsuno
Kenjiro
K
Toda
Etsuko
E
Nishiwaki
Tetsu
T
Matsuo
Naoki
N
Nakano
Akiko
A
Narumi
Shosaku
S
Lu
Bao
B
Gerard
Craig
C
Ishikawa
Sho
S
Matsushima
Kouji
K
D000818:Animals; D018801:CD2 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D020566:Dendritic Cells, Follicular / Q000276:immunology* / Q000821:virology; D005260:Female; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010950:Plasma Cells / Q000276:immunology*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014779:Virus Replication / Q000235:genetics
D018801:CD2 Antigens; C515187:CXCR3 protein, human; C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D023201:CD40 Ligand