Nagaraju K, Raben N, Villalba M L, Danning C, Loeffler L A, Lee E, Tresser N, Abati A, Fetsch P, Plotz P H
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, 20892-1820, USA.
Clin Immunol. 1999 Aug;92(2):161-9. doi: 10.1006/clim.1999.4743.
In an attempt to understand the mechanisms of cell injury in the inflammatory myopathies, we analyzed the expression of costimulatory molecules, CTLA4, CD28, CD86, CD40, and CD154 as well as HLA class I, HLA class II, and ICAM-I in normal muscle and in muscle biopsies from patients with polymyositis (PM) or dermatomyositis (DM). By immunohistochemical staining, DM and PM biopsies showed the presence of CTLA4, CD28, CD86, and CD40 on inflammatory cells. More strikingly, however, low levels of CTLA4 and CD28 were observed on muscle cells. The expression of CTLA4 and CD28 on nonlymphoid cells has not been previously reported. These unexpected findings were confirmed in cultured normal human myoblasts: various proinflammatory cytokines induced the expression of CTLA4 and CD28 on normal human muscle cells. The sequences of the cDNAs were found to be identical to the sequences for these molecules in T cells. The data suggest a novel complexity in the network of cellular interactions between the infiltrated immune cells and the muscle cells in which the normal relationship between infiltrating inflammatory cells and target tissue is under a previously unrecognized set of controls.
为了了解炎性肌病中细胞损伤的机制，我们分析了共刺激分子CTLA4、CD28、CD86、CD40和CD154以及I类人 HLA、II类人 HLA和细胞间黏附分子1（ICAM-1）在正常肌肉以及多肌炎（PM）或皮肌炎（DM）患者肌肉活检组织中的表达情况。通过免疫组织化学染色发现，DM和PM活检组织中的炎性细胞存在CTLA4、CD28、CD86和CD40。然而，更引人注目的是，在肌肉细胞上观察到CTLA4和CD28水平较低。非淋巴细胞上CTLA4和CD28的表达此前尚未见报道。在培养的正常人成肌细胞中证实了这些意外发现：多种促炎细胞因子可诱导正常人肌肉细胞表达CTLA4和CD28。发现这些cDNA的序列与T细胞中这些分子的序列相同。数据表明，浸润的免疫细胞与肌肉细胞之间的细胞相互作用网络存在一种新的复杂性，其中浸润的炎性细胞与靶组织之间的正常关系处于一组此前未被认识的控制之下。
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