Activation of influenza virus-specific CD4+ and CD8+ T cells:: a new role for plasmacytoid denchitic cells in adaptive immunity

被引:249
作者
Fonteneau, JF
Gilliet, M
Larsson, M
Dasilva, I
Münz, C
Liu, YJ
Bhardwaj, N
机构
[1] Rockefeller Univ, Mol Neurooncol Lab, New York, NY 10021 USA
[2] Rockefeller Univ, Cellular Physiol & Immunol Lab, New York, NY 10021 USA
[3] DNAX Res Inst Molec & Cellular Biol Inc, Dept Immunol, Palo Alto, CA USA
关键词
D O I
10.1182/blood-2002-10-3063
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Plasmacytoid dendritic cells (pDCs) contribute to innate antiviral immune responses by producing type I interferons (IFNs) upon exposure to enveloped viruses. However, their role in adaptive immune responses, such as the initiation of antiviral T-cell responses, is not known. In this study, we examined interactions between blood pDCs and influenza virus with special attention to the capacity of pDCs to activate influenza-specific T cells. pDCs were compared with CD11c(+) DCs, the most potent antigen-presenting cells (APCs), for their capacity to activate T-cell responses. We found that like CD11c(+) DCs, pDCs mature following exposure to influenza virus, express CCR7, and produce proinflammatory chemokines, but differ in that they produce type I IFN and are resistant to the cytopathic effect of the infection. After influenza virus exposure, both DC types exhibited an equivalent efficiency to expand anti-influenza virus cytotoxic T lymphocytes (CTLs) and T helper I (THII) CD4(+) T cells. Our results pinpoint a new role of pDCs in the induction of antiviral T-cell responses and suggest that these DCs play a prominent role in the adaptive immune response against viruses. (C) 2003 by The American Society of Hematology.
引用
收藏
页码:3520 / 3526
页数:7
相关论文
共 34 条
[1]   IFN-α and IFN-β: A link between immune memory and chronic inflammation [J].
Akbar, AN ;
Lord, JM ;
Salmon, M .
IMMUNOLOGY TODAY, 2000, 21 (07) :337-+
[2]   Mouse type IIFN-producing cells are immature APCs with plasmacytoid morphology [J].
Asselin-Paturel, C ;
Boonstra, A ;
Dalod, M ;
Durand, I ;
Yessaad, N ;
Dezutter-Dambuyant, C ;
Vicari, A ;
O'Garra, A ;
Biron, C ;
Brière, F ;
Trinchieri, G .
NATURE IMMUNOLOGY, 2001, 2 (12) :1144-1150
[3]   Dendritic cells and the control of immunity [J].
Banchereau, J ;
Steinman, RM .
NATURE, 1998, 392 (6673) :245-252
[4]   INACTIVATED INFLUENZA-VIRUS, WHEN PRESENTED ON DENDRITIC CELLS, ELICITS HUMAN CD8(+) CYTOLYTIC T-CELL RESPONSES [J].
BENDER, A ;
BUI, LK ;
FELDMAN, MAV ;
LARSSON, M ;
BHARDWAJ, N .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (06) :1663-1671
[5]   Improved methods for the generation of dendritic cells from nonproliferating progenitors in human blood [J].
Bender, A ;
Sapp, M ;
Schuler, G ;
Steinman, RM ;
Bhardwaj, N .
JOURNAL OF IMMUNOLOGICAL METHODS, 1996, 196 (02) :121-135
[6]   INFLUENZA VIRUS-INFECTED DENDRITIC CELLS STIMULATE STRONG PROLIFERATIVE AND CYTOLYTIC RESPONSES FROM HUMAN CD8+ T-CELLS [J].
BHARDWAJ, N ;
BENDER, A ;
GONZALEZ, N ;
BUI, LK ;
GARRETT, MC ;
STEINMAN, RM .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (02) :797-807
[7]   Isolation and characterization of plasmacytoid dendritic cells from Flt3 ligand and granulocyte-macrophage colony-stimulating factor-treated mice [J].
Björck, P .
BLOOD, 2001, 98 (13) :3520-3526
[8]   Plasmacytoid dendritic cells activated by influenza virus and CD40L drive a potent THI polarization [J].
Cella, M ;
Facchetti, F ;
Lanzavecchia, A ;
Colonna, M .
NATURE IMMUNOLOGY, 2000, 1 (04) :305-310
[9]   Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon [J].
Cella, M ;
Jarrossay, D ;
Facchetti, F ;
Alebardi, O ;
Nakajima, H ;
Lanzavecchia, A ;
Colonna, M .
NATURE MEDICINE, 1999, 5 (08) :919-923
[10]   Interferon α/β and interleukin 12 responses to viral infections:: Pathways regulating dendritic cell cytokine expression in vivo [J].
Dalod, M ;
Salazar-Mather, TP ;
Malmgaard, L ;
Lewis, C ;
Asselin-Paturel, C ;
Brière, F ;
Trinchieri, G ;
Biron, CA .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 195 (04) :517-528