PD-1 ligands, negative regulators for activation of naive, memory, and recently activated human CD4+ T cells

被引:62
作者
Cai, GF
Karni, A
Oliveira, EML
Weiner, HL
Hafler, DA
Freeman, GJ
机构
[1] Brigham & Womens Hosp, Dept Neurol, Lab Mol Immunol, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
关键词
PD-1; ligand; costimulation; dendritic cells; human T cells; naive T cells; memory T cells; myelin basic protein;
D O I
10.1016/j.cellimm.2004.09.004
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We examined the role of the PD-1 pathway on the activation of naive, memory, and recently activated human CD4(+) T cells to test whether they responded differently. PD-1 ligand blockade modestly enhanced the percentage of responding T cells and production of IFN-gamma in a primary response to myelin basic protein (MBP) in normal donors. PD-1 ligand blockade strongly enhanced proliferation and cytokine production by memory or recently activated T cells (tetanus toxoid and MBP). Blockade of PD-L1 alone had more effect than PD-L2, consistent with its higher expression on ex vivo dendritic cells; furthermore, anti-PD-L1 plus anti-PD-L2 resulted in the greatest enhancement. Moreover, PD-L1-Ig inhibited anti-CD3 induced activation of naive, memory, and recently activated CD4+ T cells. Together, our data demonstrated PD-1 functioned as a negative regulatory pathway on naive T cells during a primary response, and more potently, on memory or recently activated T cells during a secondary response. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:89 / 98
页数:10
相关论文
共 44 条
  • [11] Coligan J.E., 1994, Current protocols in immunology
  • [12] Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity
    Curiel, TJ
    Wei, S
    Dong, HD
    Alvarez, X
    Cheng, P
    Mottram, P
    Krzysiek, R
    Knutson, KL
    Daniel, B
    Zimmermann, MC
    David, O
    Burow, M
    Gordon, A
    Dhurandhar, N
    Myers, L
    Berggren, R
    Hemminki, A
    Alvarez, RD
    Emilie, D
    Curiel, DT
    Chen, LP
    Zou, WP
    [J]. NATURE MEDICINE, 2003, 9 (05) : 562 - 567
  • [13] Angiopoietins have distinct modular domains essential for receptor binding, dimerization and superclustering
    Davis, S
    Papadopoulos, N
    Aldrich, TH
    Maisonpierre, PC
    Huang, T
    Kovac, L
    Xu, A
    Leidich, R
    Radziejewska, E
    Rafique, A
    Goldberg, J
    Jain, V
    Bailey, K
    Karow, M
    Fandl, J
    Samuelsson, SJ
    Ioffe, E
    Rudge, JS
    Daly, TJ
    Radziejewski, C
    Yancopoulos, GD
    [J]. NATURE STRUCTURAL BIOLOGY, 2003, 10 (01) : 38 - 44
  • [14] LARGE-SCALE PREPARATION OF MYELIN BASIC PROTEIN FROM CENTRAL NERVOUS-TISSUE OF SEVERAL MAMMALIAN SPECIES
    DEIBLER, GE
    KIES, MW
    MARTENSON, RE
    [J]. PREPARATIVE BIOCHEMISTRY, 1972, 2 (02): : 139 - +
  • [15] Costimulating aberrant T cell responses by B7-H1 autoantibodies in rheumatoid arthritis
    Dong, HD
    Strome, SE
    Matteson, EL
    Moder, KG
    Flies, DB
    Zhu, GF
    Tamura, H
    Driscoll, CLW
    Chen, LP
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2003, 111 (03) : 363 - 370
  • [16] Dong HD, 1999, NAT MED, V5, P1365
  • [17] Dong HD, 2002, NAT MED, V8, P793, DOI 10.1038/nm730
  • [18] Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation
    Freeman, GJ
    Long, AJ
    Iwai, Y
    Bourque, K
    Chernova, T
    Nishimura, H
    Fitz, LJ
    Malenkovich, N
    Okazaki, T
    Byrne, MC
    Horton, HF
    Fouser, L
    Carter, L
    Ling, V
    Bowman, MR
    Carreno, BM
    Collins, M
    Wood, CR
    Honjo, T
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (07) : 1027 - 1034
  • [19] Differential expression of PD-L1 and PD-L2, ligands for an inhibitory receptor PD-1, in the cells of lymphohematopoietic tissues
    Ishida, M
    Iwai, Y
    Tanaka, Y
    Okazaki, T
    Freeman, GJ
    Minato, N
    Honjo, T
    [J]. IMMUNOLOGY LETTERS, 2002, 84 (01) : 57 - 62
  • [20] THE COEXPRESSION OF CD45RA AND CD45RO ISOFORMS ON T-CELLS DURING THE S/G2/M STAGES OF CELL-CYCLE
    LASALLE, JM
    HAFLER, DA
    [J]. CELLULAR IMMUNOLOGY, 1991, 138 (01) : 197 - 206