Cutting edge: Induced indoleamine 2,3 dioxygenase expression in dendritic cell subsets suppresses T cell clonal expansion

被引:373
作者
Mellor, AL
Baban, B
Chandler, P
Marshall, B
Jhaver, K
Hansen, A
Koni, PA
Iwashima, M
Munn, DH
机构
[1] Med Coll Georgia, Inst Mol Med & Genet, Program Mol Immunol, Dept Med, Augusta, GA 30912 USA
[2] Med Coll Georgia, Inst Mol Med & Genet, Program Mol Immunol, Dept Pediat, Augusta, GA 30912 USA
[3] Lexicon Genet, The Woodlands, TX 77381 USA
[4] Res Ctr Allergy & Immunol, Inst Phys & Chem Res, Tsurumi Ku, Yokohama, Kanagawa, Japan
关键词
D O I
10.4049/jimmunol.171.4.1652
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In mice, immunoregulatory APCs express the dendritic cell (DC) marker CD11c, and one or more distinctive markers (CD8alpha, B220, DX5). In this study, we show that expression of the tryptophan-degrading enzyme indoleamine 2,3 dioxygenase (IDO) is selectively induced in specific splenic DC subsets when mice were exposed to the synthetic immunomodulatory reagent CTLA4-Ig. CTLA4-Ig did not induce IDO expression in macrophages or lymphoid cells. Induction of IDO completely blocked clonal expansion of T cells from TCR transgenic mice following adoptive transfer, whereas CTLA4-Ig treatment did not block T cell clonal expansion in IDO-deficient recipients. Thus, IDO expression is an inducible feature of specific subsets of DO, and provides a potential mechanistic explanation for their T cell regulatory properties.
引用
收藏
页码:1652 / 1655
页数:4
相关论文
共 34 条
  • [1] The CD8α+ dendritic cell is responsible for inducing peripheral self-tolerance to tissue-associated antigens
    Belz, GT
    Behrens, GMN
    Smith, CM
    Miller, JFAP
    Jones, C
    Lejon, K
    Fathman, CG
    Mueller, SN
    Shortman, K
    Carbone, FR
    Heath, WR
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (08) : 1099 - 1104
  • [2] Bodaghi B, 1999, J IMMUNOL, V162, P957
  • [3] Constitutive versus activation-dependent cross-presentation of immune complexes by CD8+ and CD8- dendritic cells in vivo
    den Haan, JMM
    Bevan, MJ
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (06) : 817 - 827
  • [4] CD8+ but not CD8- dendritic cells cross-prime cytotoxic T cells in vivo
    den Haan, JMM
    Lehar, SM
    Bevan, MJ
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (12) : 1685 - 1695
  • [5] Functional expression of indoleamine 2,3-dioxygenase by murine CD8α+ dendritic cells
    Fallarino, F
    Vacca, C
    Orabona, C
    Belladonna, ML
    Bianchi, R
    Marshall, B
    Keskin, DB
    Mellor, AL
    Fioretti, MC
    Grohmann, U
    Puccetti, P
    [J]. INTERNATIONAL IMMUNOLOGY, 2002, 14 (01) : 65 - 68
  • [6] Indoleamine 2,3-dioxygenase contributes to tumor cell evasion of T cell-mediated rejection
    Friberg, M
    Jennings, R
    Alsarraj, M
    Dessureault, S
    Cantor, A
    Extermann, M
    Mellor, AL
    Munn, DH
    Antonia, SJ
    [J]. INTERNATIONAL JOURNAL OF CANCER, 2002, 101 (02) : 151 - 155
  • [7] T cell proliferation is blocked by indoleamine 2,3-dioxygenase
    Frumento, G
    Rotondo, R
    Tonetti, M
    Ferrara, GB
    [J]. TRANSPLANTATION PROCEEDINGS, 2001, 33 (1-2) : 428 - 430
  • [8] IMMUNE ACTIVATION AND DECREASED TRYPTOPHAN IN PATIENTS WITH HIV-1 INFECTION
    FUCHS, D
    FORSMAN, A
    HAGBERG, L
    LARSSON, M
    NORKRANS, G
    REIBNEGGER, G
    WERNER, ER
    WACHTER, H
    [J]. JOURNAL OF INTERFERON RESEARCH, 1990, 10 (06): : 599 - 603
  • [9] The development of murine plasmacytoid dendritic cell precursors is differentially regulated by FLT3-ligand and granulocyte/macrophage colony-stimulating factor
    Gilliet, M
    Boonstra, A
    Paturel, C
    Antonenko, S
    Xu, XL
    Trinchieri, G
    O'Garra, A
    Liu, YJ
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 195 (07) : 953 - 958
  • [10] CTLA-4-Ig regulates tryptophan catabolism in vivo
    Grohmann, U
    Orabona, C
    Fallarino, F
    Vacca, C
    Calcinaro, F
    Falorni, A
    Candeloro, P
    Belladonna, ML
    Bianchi, R
    Fioretti, MC
    Puccetti, P
    [J]. NATURE IMMUNOLOGY, 2002, 3 (11) : 1097 - 1101