Interferon-γ plays a nonredundant role in mediating T-cell-dependent outward vascular remodeling of allogeneic human coronary arteries

被引:64
作者
Wang, YN
Burns, WR
Tang, PCY
Yi, T
Schechner, JS
Zerwes, HG
Sessa, WC
Lorber, MI
Pober, JS
Tellides, G
机构
[1] Yale Univ, Sch Med, Interdept Program Vasc Biol & Transplantat, New Haven, CT 06510 USA
[2] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA
[3] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA
[4] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA
[5] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06510 USA
[6] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA
[7] Novartis Pharma AG, CH-4002 Basel, Switzerland
关键词
arteriosclerosis; T cells; cytokines; vascular smooth muscle cells;
D O I
10.1096/fj.03-0840fje
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Vascular remodeling (change in vessel diameter) rather than intimal hyperplasia is the most important predictor of luminal loss in immune-mediated arterial injury, yet little is known about its mechanisms. Here, we show that outward vascular remodeling and intimal thickening, two manifestations of arteriosclerosis with opposing effects on luminal size, result from immune effector mechanisms that are T-cell dependent and interferon (IFN)-gamma mediated. In our in vivo model of human coronary artery injury by allogeneic peripheral blood mononuclear cells, both processes occur concurrently and are characterized by T-cell infiltrates with a predominantly IFN-gamma-producing cytokine profile. Neutralization of IFN-gamma inhibits the arterial and intimal expansion, whereas administration of IFN-gamma enhances these effects. The nonredundant role of IFN-gamma in T-cell-dependent remodeling of human coronary arteries demonstrated here presents a new therapeutic target for preservation of vessel lumen in arteriosclerosis.
引用
收藏
页码:606 / +
页数:19
相关论文
共 42 条
  • [1] Functional diversity of helper T lymphocytes
    Abbas, AK
    Murphy, KM
    Sher, A
    [J]. NATURE, 1996, 383 (6603) : 787 - 793
  • [2] Transplantation-induced endothelial dysfunction as studied in rat aorta allografts
    Andriambeloson, E
    Pally, C
    Hengerer, B
    Cannet, C
    Nikolova, Z
    Bruns, C
    Zerwes, HG
    Bigaud, M
    [J]. TRANSPLANTATION, 2001, 72 (12) : 1881 - 1889
  • [3] T helper type 1 lymphocytes drive inflammation in human atherosclerotic lesions
    Benagiano, M
    Azzurri, A
    Ciervo, A
    Amedei, A
    Tamburini, C
    Ferrari, M
    Telford, JL
    Baldari, CT
    Romagnani, S
    Cassone, A
    D'Elios, MM
    Del Prete, G
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (11) : 6658 - 6663
  • [4] CARDIAC TRANSPLANTATION IN MAN .7. CARDIAC ALLOGRAFT PATHOLOGY
    BIEBER, CP
    STINSON, EB
    SHUMWAY, NE
    PAYNE, R
    KOSEK, J
    [J]. CIRCULATION, 1970, 41 (05) : 753 - &
  • [5] Cellular responses to interferon-gamma
    Boehm, U
    Klamp, T
    Groot, M
    Howard, JC
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 : 749 - 795
  • [6] GENERATION OF POLARIZED ANTIGEN-SPECIFIC CD8 EFFECTOR POPULATIONS - RECIPROCAL ACTION OF INTERLEUKIN (IL)-4 AND IL-12 IN PROMOTING TYPE-2 VERSUS TYPE-1 CYTOKINE PROFILES
    CROFT, M
    CARTER, L
    SWAIN, SL
    DUTTON, RW
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (05) : 1715 - 1728
  • [7] IFN-γ action in the media of the great elastic arteries, a novel immunoprivileged site
    Dal Canto, AJ
    Swanson, PE
    O'Guin, AK
    Speck, SH
    Virgin, HW
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (02) : R15 - R22
  • [8] Dong CM, 1996, LAB INVEST, V74, P921
  • [9] RESPONSES OF CORONARY-ARTERIES OF CARDIAC TRANSPLANT PATIENTS TO ACETYLCHOLINE
    FISH, RD
    NABEL, EG
    SELWYN, AP
    LUDMER, PL
    MUDGE, GH
    KIRSHENBAUM, JM
    SCHOEN, FJ
    ALEXANDER, RW
    GANZ, P
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1988, 81 (01) : 21 - 31
  • [10] Cytokine expression in advanced human atherosclerotic plaques:: dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines
    Frostegård, J
    Ulfgren, AK
    Nyberg, P
    Hedin, U
    Swedenborg, J
    Andersson, U
    Hansson, GK
    [J]. ATHEROSCLEROSIS, 1999, 145 (01) : 33 - 43