Cytokine secretion of myelin basic protein reactive T cells in patients with multiple sclerosis
Cytokine secretion of myelin basic protein reactive T cells in patients with multiple sclerosis
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DOI：
10.1016/s0165-5728(98)00086-1
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发表时间：
1998-11-02
影响因子：
3.3
通讯作者：
Hafler, DA
中科院分区：
文献类型：
--
作者：
Windhagen, A;Anderson, DE;Hafler, DA
本研究的目的是确定多发性硬化症（MS）患者的自身反应性T细胞在分化为稳定的细胞因子表型时是否极化且定型，或者细胞因子的分泌是否可以改变。我们检测了12例复发缓解型MS（RR - MS）患者、9例慢性进展型MS（CP - MS）患者和14名正常个体中髓鞘碱性蛋白（MBP）反应性T细胞与破伤风类毒素反应性（TT）T细胞所分泌的细胞因子。在促进Th1（IL - 12/抗IL - 4单克隆抗体）或Th2（IL - 4/抗IL - 12单克隆抗体）细胞因子分泌的生长条件下，共产生了5094个针对MBP和TT的短期T细胞系。正常人和MS患者的抗原特异性细胞因子分泌可根据培养条件转变为Th1或Th2型表型，这表明即使在长期的慢性进展型MS中，MBP反应性T细胞的表型也可改变。MS患者的MBP反应性T细胞所分泌的细胞因子模式与正常个体相比无显著差异。然而，与正常对照和RR - MS相比，CP - MS患者在使用IL - 12/抗IL - 4单克隆抗体培养时，分泌IL - 4的MBP反应性T细胞往往较少，而在使用IL - 4/抗IL - 12单克隆抗体培养时，分泌干扰素 - γ的MBP反应性T细胞较多，这表明这些患者的细胞可能更极化，或者这些个体中未分化的MBP反应性细胞较少。最显著的观察结果是，与RR - MS患者和正常对照不同，在CP - MS中分泌细胞因子的MBP反应性T细胞几乎没有一个掺入（³H）胸腺嘧啶核苷。这可能是由于在IL - 12存在的情况下体内长期受到刺激，或者是因为这些T细胞可能已进入终末分化状态。尽管如此，即使在长期的自身免疫性疾病中也能改变自身反应性T细胞系的细胞因子分泌，这表明细胞因子疗法通过改变髓鞘反应性T细胞的功能使其无致病性，可能具有治疗益处。（C）1998爱思唯尔科学出版社。版权所有。
The objective of this study was to determine whether autoreactive T cells in patients with multiple sclerosis (MS) are polarized and committed in their differentiation to a stable cytokine phenotype or whether the cytokine secretion can be altered. We examined the cytokines secreted by myelin basic protein (MBP) as compared to tetanus toroid-reactive (TT)T cells in 12 patients with relapsing remitting MS (RR-MS), 9 patients with chronic progressive MS (CP-MS), and 14 normal individuals. A total of 5094 short term T cell lines to MBP and TT were generated in the presence of growth conditions promoting Th1 (IL-12/alpha-IL-4 mAb) or Th2 (IL-4/alpha-IL-12 mAb) cytokine secretion. Antigen-specific cytokine secretion from normals and MS patients could be shifted to a Th1 or Th2 type phenotype depending upon culture conditions, indicating that the phenotype of MBP reactive T cells can be altered even in longstanding chronic progressive MS. There were no significant differences in the cytokine patterns secreted by MBP reactive T cells in patients with MS as compared to normal individuals. However, CP-MS patients tended to have fewer MBP reactive T cells secreting IL-4 when cultured with IL-12/anti-IL-4 mAb and more IFN-gamma secreting MBP reactive T cells when cultured with IL-4/anti-IL-12 mAb as compared to both normal controls and RR-MS, suggesting that cells from these patients might be more polarized or that fewer undifferentiated MBP-reactive cells are present in these individuals. The most striking observation was that in contrast to the RR-MS patients and normal controls, almost none of the MBP reactive T cells secreting cytokines in CP-MS incorporated (3)[H]thymidine. This may be due to chronic in vivo stimulation in the presence of IL-12, or because these T cells may have entered a terminally differentiated state. Nonetheless, the ability to alter the cytokine secretion of autoreactive T cell lines even in longstanding autoimmune disease indicates that cytokine therapy might have therapeutic benefits by switching the function of myelin reactive T cells such that they are non-pathogenic. (C) 1998 Elsevier Science B.V. All rights reserved.