Correale Jorge, de los Milagros Bassani Molinas María
Department of Neurology, Raúl Carrea Institute for Neurological Research (FLENI), Montañeses 2325, Buenos Aires 1428, Argentina.
J Neuroimmunol. 2003 Mar;136(1-2):162-71. doi: 10.1016/s0165-5728(03)00035-3.
CD4(+) T-cell lines (TCLs) from patients with clinically isolated syndromes (CIS) were selected with purified human myelin basic protein (MBP) and recombinant human myelin oligodendrocyte glycoprotein (rhMOG), at onset of neurological symptoms and when patients developed clinically definite multiple sclerosis (CDMS). The epitope specificity of each TCL was mapped with overlapping synthetic peptides. TCLs were assessed for their ability to secrete IFN-gamma, IL-4, and IL-6. Diverse patterns of epitope recognition were observed: (a) recognition of a broad spectrum of MBP peptide epitopes with evidence of shifts over time; (b) an initial T-cell response focused to a restricted segment of the MBP molecule (83-102) that broadened over the course of disease; and (c) persistence of a focused anti-MOG T-cell response. CIS patients who failed to develop CDMS maintained a focused epitope response against two to six MBP epitopes. Most MBP peptide-specific TCLs secreted considerable amounts of IFN-gamma and low amounts of IL-4 and IL-6, whereas anti rhMOG(Igd) peptide-specific TCLs secreted preferentially IL-4 and IL-6. These data raise important issues for the pathogenesis and treatment of multiple sclerosis (MS).
在神经症状出现时以及患者发展为临床确诊的多发性硬化症（CDMS）时，从临床孤立综合征（CIS）患者中选取CD4(+) T细胞系（TCLs），并用纯化的人髓鞘碱性蛋白（MBP）和重组人髓鞘少突胶质细胞糖蛋白（rhMOG）进行筛选。用重叠合成肽绘制每个TCL的表位特异性图谱。评估TCLs分泌γ干扰素、白细胞介素-4和白细胞介素-6的能力。观察到不同的表位识别模式：（a）识别广泛的MBP肽表位，且有随时间变化的证据；（b）最初的T细胞反应集中于MBP分子的一个受限片段（83-102），该片段在疾病过程中会扩大；（c）针对MOG的T细胞反应持续集中。未发展为CDMS的CIS患者维持针对两到六个MBP表位的集中表位反应。大多数MBP肽特异性TCLs分泌大量的γ干扰素和少量的白细胞介素-4和白细胞介素-6，而抗rhMOG(Igd)肽特异性TCLs优先分泌白细胞介素-4和白细胞介素-6。这些数据为多发性硬化症（MS）的发病机制和治疗提出了重要问题。
