Membrane bound IL-15 is increased on CD14 monocytes in early stages of MS

被引:21
作者
Vaknin-Dembinsky, Adi [1 ]
Brass, Steven [1 ]
Gandhi, Roopali [1 ]
Weiner, Howard L. [1 ]
机构
[1] Brigham & Womens Hosp, Ctr Neurol Dis, Harvard Med Sci, Boston, MA 02115 USA
关键词
multiple sclerosis; IL-15; monocytes;
D O I
10.1016/j.jneuroim.2008.01.016
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
IL-15 is a pro-inflammatory cytokine whose three-dimensional structure is similar to that of IL-2. IL-2 and IL-15 have similar as well as distinct biological functions. An active form of IL-15 that is membrane bound has also been described. Furthermore, IL-15 is known to play a role in autoimmune diseases. We thus investigated the expression of membrane bound IL-15 on monocytes (CD14+ cells) and studied its effect on T cell activation in MS patients. We found that unstimulated CD14+ cells from relapsing remitting MS patients had increased membrane bound IL-15. Those with high surface levels of IL-15 on monocytes were in the early stages of the disease. In addition, we found that T cells of MS patients had enhanced responsiveness to IL-15 and there was increased expression of IL-15 receptor on CD4+ T cells. Thus, I L-15 may bean important cytokine that drives Th1 responses early in the course of the disease and could serve as a target for immunotherapy and as an early marker in the immunologic staging of MS. (C) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:135 / 139
页数:5
相关论文
共 33 条
[1]  
Agostini C, 1996, J IMMUNOL, V157, P910
[2]   Increased interleukin 12 production in progressive multiple sclerosis: Induction by activated CD4(+) T cells via CD40 ligand [J].
Balashov, KE ;
Smith, DR ;
Khoury, SJ ;
Hafler, DA ;
Weiner, HL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (02) :599-603
[3]   IL-15 and IL-15R in leucocytes from patients with systemic lupus erythematosus [J].
Baranda, L ;
de la Fuente, H ;
Layseca-Espinosa, E ;
Portales-Pérez, D ;
Niño-Moreno, P ;
Valencia-Pacheco, G ;
Abud-Mendoza, C ;
Alcocer-Varela, J ;
González-Amaro, R .
RHEUMATOLOGY, 2005, 44 (12) :1507-1513
[4]   Transcriptional analysis of multiple sclerosis brain lesions reveals a complex pattern of cytokine expression [J].
Baranzini, SE ;
Elfstrom, C ;
Chang, SY ;
Butunoi, C ;
Murray, R ;
Higuchi, R ;
Oksenberg, JR .
JOURNAL OF IMMUNOLOGY, 2000, 165 (11) :6576-6582
[5]   TH-17 cells in the circle of immunity and autoimmunity [J].
Bettelli, Estelle ;
Oukka, Mohamed ;
Kuchroo, Vijay K. .
NATURE IMMUNOLOGY, 2007, 8 (04) :345-350
[6]   Interleukin-15 protects from lethal apoptosis in vivo [J].
BulfonePaus, S ;
Ungureanu, D ;
Pohl, T ;
Lindner, G ;
Paus, R ;
Ruckert, R ;
Krause, H ;
Kunzendorf, U .
NATURE MEDICINE, 1997, 3 (10) :1124-1128
[7]   Endogenous production of interleukin 15 by activated human monocytes is critical for optimal production of interferon-gamma by natural killer cells in vitro [J].
Carson, WE ;
Ross, ME ;
Baiocchi, RA ;
Marien, MJ ;
Boiani, N ;
Grabstein, K ;
Caligiuri, MA .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (06) :2578-2582
[8]   IDENTIFICATION AND CLONING OF A NOVEL IL-15 BINDING-PROTEIN THAT IS STRUCTURALLY RELATED TO THE ALPHA-CHAIN OF THE IL-2 RECEPTOR [J].
GIRI, JG ;
KUMAKI, S ;
AHDIEH, M ;
FRIEND, DJ ;
LOOMIS, A ;
SHANEBECK, K ;
DUBOSE, R ;
COSMAN, D ;
PARK, LS ;
ANDERSON, DM .
EMBO JOURNAL, 1995, 14 (15) :3654-3663
[9]   UTILIZATION OF THE BETA-CHAIN AND GAMMA-CHAIN OF THE IL-2 RECEPTOR BY THE NOVEL CYTOKINE-IL-15 [J].
GIRI, JG ;
AHDIEH, M ;
EISENMAN, J ;
SHANEBECK, K ;
GRABSTEIN, K ;
KUMAKI, S ;
NAMEN, A ;
PARK, LS ;
COSMAN, D ;
ANDERSON, D .
EMBO JOURNAL, 1994, 13 (12) :2822-2830
[10]   Interleukin-15 and interferon-γ participate in the cross-talk between natural killer and monocytic cells required for tumour necrosis factor production [J].
Gonzalez-Alvaro, Isidoro ;
Dominguez-Jimenez, Carmen ;
Ortiz, Ana M. ;
Nunez-Gonzalez, Vanessa ;
Roda-Navarro, Pedro ;
Fernandez-Ruiz, Elena ;
Sancho, David ;
Sanchez-Madrid, Francisco .
ARTHRITIS RESEARCH & THERAPY, 2006, 8 (04)