Monocyte-derived IL12, CD86 (B7-2) and CD40L expression in relapsing and progressive multiple sclerosis
Monocyte-derived IL12, CD86 (B7-2) and CD40L expression in relapsing and progressive multiple sclerosis
复制标题
DOI：
10.1016/s1521-6616(02)00028-1
复制
发表时间：
2003-02-01
影响因子：
8.6
通讯作者：
Freedman, MS
中科院分区：
文献类型：
--
作者：
Filion, LG;Matusevicius, D;Freedman, MS
多发性硬化症被认为是一种自身免疫性疾病，其中Th 1免疫反应占主导地位。该应答与分别由T细胞和单核细胞（MO）谱系的细胞产生的IFN γ和IL 12的产生增加有关。还观察到T细胞和抗原呈递细胞的共刺激分子的表达增加。我们假设在复发缓解型MS（RRMS）（有或没有IFN β治疗）和继发进展型患者（SPMS）中，IL 12和共刺激分子（CD 80 [B7-1]、CD 86 [B7-2]、CD 28、CD 40、CD 40 L）将由MO或T细胞差异地产生或表达。我们对SPMS或未经治疗和IFN-γ治疗的RRMS患者的外周血单核细胞（PBMC）或MO进行了横断面和纵向流式细胞术研究（每月一次）。我们确定，CD 86和CD 40 L的表达是最高的MO来自SPMS患者相比，从RRMS或健康对照（HC）。与来源于SPMS或HC的细胞相比，在PBMC与重组人IL 10（一种可响应于IFN β治疗而增加并下调CD 86表达的细胞因子）的体外培养中，来源于RRMS患者的MO上的CD 86表达降低的程度高得多。来自SPMS患者的新鲜分离的MO的体外分泌的IL 12水平比治疗或未治疗的RRMS或HC高10倍以上。用IFN β治疗的RRMS患者表现出略低的MO IL 12分泌水平。我们的数据表明，MS发病机制中的一个关键机制是疾病进展过程中CD 86和CD 40 L表达增加以及IL 12产生增加。IFN β的部分作用机制可能是减少MO CD 86和CD 40 L表达以及IL 12分泌;未能这样做可能意味着缺乏反应或向疾病的更进展阶段过渡。(C)2003 Elsevier Science（美国）。All rights reserved.
Multiple sclerosis has been postulated to be an autoimmune disease in which Th1 immune responses predominate. This response is associated with an increased production of IFNgamma and IL12 produced by T cells and by cells of the monocyte (MO) lineage, respectively. An increased expression of costimulatory molecules by T cells and antigen-presenting cells is also observed. We hypothesized that in relapsing-remitting MS (RRMS) (with or without of IFNbeta treatment) and in secondary progressive patients (SPMS) IL12 and costimulatory molecules (CD80 [B7-1], CD86 [B7-2], CD28, CD40, CD40L) would be differentially produced or expressed by MO or T cells. We performed cross-sectional and longitudinal flow cytometric studies (at monthly intervals) on peripheral blood mononuclear cells (PBMC) or on MO from SPMS or untreated and IFNP-treated patients with RRMS. We determined that CD86 and CD40L expression was highest on MO derived from SPMS patients compared to those from RRMS or from healthy controls (HC). In vitro culture of PBMC with recombinant human IL10, a cytokine that may be increased in response to treatment with IFNbeta and that down-regulates CD86 expression, reduced the expression of CD86 on MO derived from RRMS patients to a much higher degree compared to cells derived from SPMS or HC. In vitro secreted IL12 levels from freshly isolated MO from SPMS patients were more than 10-fold higher than either the treated or the untreated RRMS or HC. RRMS patients treated with IFNbeta demonstrated slightly lower levels of MO IL12 secretion. Our data suggest that a key mechanism in the pathogenesis of MS is the increased expression of CD86 and CD40L and the increased production of IL12 during disease progression. Part of the mechanism of action of IFNbeta may be to reduce MO CD86 and CD40L expression and IL12 secretion; failure to do so might signify either a lack of response or a transition to a more progressive phase of illness. (C) 2003 Elsevier Science (USA). All rights reserved.