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活动性多发性硬化症患者T细胞系抗炎细胞因子转化生长因子-β(TGF-β)产生缺陷。

Defective production of anti-inflammatory cytokine, TGF-beta by T cell lines of patients with active multiple sclerosis.

作者信息

Mokhtarian F, Shi Y, Shirazian D, Morgante L, Miller A, Grob D

机构信息

Department of Medicine, Maimonides Medical Center, Brooklyn, NY 11219.

出版信息

J Immunol. 1994 Jun 15;152(12):6003-10.

PMID:8207225
Abstract

Activated T lymphocytes play an important role in the pathogenesis of multiple sclerosis (MS). These T cells secrete both pro- and anti-inflammatory cytokines. We have studied the production of these two kinds of cytokines by PBL of patients with MS and compared it with normal controls and other autoimmune diseases (OAD). PBL of 29 patients with MS, 14 patients with OAD, and 14 healthy normal controls were cultured for 5 wk. PBL of MS patients produced more pro-inflammatory cytokines, IL-2, IFN-gamma and TNF/lymphotoxin, and less anti-inflammatory cytokine, TGF-beta, during wk 2 to 4 in culture than PBL of normal controls. PBL of MS patients also produced more IL-2 and TNF/lymphotoxin than PBL of OAD patients. Decreased TGF-beta production by lymphocytes of patients with MS correlated directly with disease activity. MS patients with active disease produced less TGF-beta than MS patients with stable disease. The cells producing TGF-beta were primarily CD8+ T cells and CD45RA+T cells. These findings emphasize the complexity of immune response in MS patients and suggest that the increased production of pro-inflammatory cytokines by lymphocytes of patients with MS, combined with the decreased production of TGF-beta (anti-inflammatory cytokine), may play an important role in the mechanisms and manifestations of MS.

摘要

活化的T淋巴细胞在多发性硬化症(MS)的发病机制中起重要作用。这些T细胞分泌促炎和抗炎细胞因子。我们研究了MS患者外周血淋巴细胞(PBL)中这两种细胞因子的产生情况,并将其与正常对照和其他自身免疫性疾病(OAD)进行比较。29例MS患者、14例OAD患者和14名健康正常对照的PBL培养5周。在培养的第2至4周,MS患者的PBL比正常对照的PBL产生更多的促炎细胞因子,如白细胞介素-2(IL-2)、干扰素-γ(IFN-γ)和肿瘤坏死因子/淋巴毒素,而抗炎细胞因子转化生长因子-β(TGF-β)产生较少。MS患者的PBL比OAD患者的PBL产生更多的IL-2和肿瘤坏死因子/淋巴毒素。MS患者淋巴细胞产生的TGF-β减少与疾病活动直接相关。处于活动期的MS患者比病情稳定的MS患者产生的TGF-β更少。产生TGF-β的细胞主要是CD8 + T细胞和CD45RA + T细胞。这些发现强调了MS患者免疫反应的复杂性,并表明MS患者淋巴细胞促炎细胞因子产生增加,同时抗炎细胞因子TGF-β产生减少,可能在MS的发病机制和表现中起重要作用。

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