Selmaj K, Raine C S, Cannella B, Brosnan C F
Albert Einstein College of Medicine, Department of Pathology (Neuropathology), Bronx, New York 10461.
J Clin Invest. 1991 Mar;87(3):949-54. doi: 10.1172/JCI115102.
Multiple sclerosis (MS) brain tissue, spleen, and PBMC were studied using immunocytochemistry and FACS for immunoreactivity for lymphotoxin (LT) and TNF. Both cytokines were identified in acute and chronic active MS lesions but were absent from chronic silent lesions. LT was associated with CD3+ lymphocytes and Leu-M5+ microglia cells at the lesion edge and to a lesser extent, in adjacent white matter. TNF was associated with astrocytes in all areas of the lesion, and with foamy macrophages in the center of the active lesion. In acute lesions, immunoreactivity for TNF in endothelial cells was noted at the lesion edge. No LT or TNF reactivity was detected in Alzheimer's or Parkinson's disease brain tissues but was present at lower levels in central nervous system (CNS) tissue from other inflammatory conditions, except for adrenoleucodystrophy which displayed high levels of LT in microglia. No increase in LT and TNF reactivity was detected in spleen and PBMC of MS patients suggesting specific reactivity within the CNS. These results indicate that LT and TNF may be involved in the immunopathogenesis of MS, and can be detected in both inflammatory cells and cells endogenous to the CNS.
采用免疫细胞化学和荧光激活细胞分选术（FACS）对多发性硬化症（MS）患者的脑组织、脾脏和外周血单核细胞（PBMC）进行研究，以检测淋巴毒素（LT）和肿瘤坏死因子（TNF）的免疫反应性。在急性和慢性活动性MS病变中均发现了这两种细胞因子，但在慢性静止性病变中未发现。LT与病变边缘的CD3 +淋巴细胞和Leu-M5 +小胶质细胞相关，在相邻白质中相关性较弱。TNF与病变所有区域的星形胶质细胞以及活动性病变中心的泡沫状巨噬细胞相关。在急性病变中，在病变边缘的内皮细胞中观察到TNF的免疫反应性。在阿尔茨海默病或帕金森病脑组织中未检测到LT或TNF反应性，但在其他炎症性疾病的中枢神经系统（CNS）组织中反应性较低，肾上腺脑白质营养不良除外，其小胶质细胞中LT水平较高。在MS患者的脾脏和PBMC中未检测到LT和TNF反应性增加，提示CNS内存在特异性反应。这些结果表明，LT和TNF可能参与MS的免疫发病机制，并且可以在炎症细胞和CNS内源性细胞中检测到。
