Whitham R H, Vandenbark A A, Bourdette D N, Chou Y K, Offner H
Veterans Administration Medical Center, Portland, Oregon 97207.
Cell Immunol. 1990 Apr 1;126(2):290-303. doi: 10.1016/0008-8749(90)90322-i.
Chronic relapsing experimental allergic encephalomyelitis (CR-EAE) can be adoptively transferred using myelin basic protein (BP)-specific helper T cell lines, and suppressor cells may be important in recovery from EAE. In order to generate suppressor cells, spleen cells obtained from BP-complete Freund's adjuvant (CFA) inoculated SJL/J mice and from normal mice were cultured for 7 days with medium, with cyclosporin A (CsA), or with CsA and antigen (BP or purified protein derivative of mycobacterium (PPD)). Cultured spleen cells were assayed for suppressor activity in vitro by coculture with BP-specific and PPD-specific helper T cell lines derived from SJL/J mice. Immunized donor spleen cells cultured with cyclosporin A (CsA) and BP were potent inhibitors of T cell line proliferation, and suppressor activity was increased 17-fold compared with control splenocytes. The number of suppressor cells required to suppress PPD-specific line proliferation by 50% (I50) was significantly higher than the number required to suppress BP-specific line proliferation, suggesting an antigen-specific component to the suppression. The major effector cell required for suppression was a large granular Mac-1+ cell with the functional characteristics of a macrophage. Suppressor activity persisted after depletion of Thy 1.2+ cells, but suppression was no longer antigen-specific, suggesting that culture of spleen cells with CsA and BP may generate suppressor macrophages which are antigen-nonspecific and Thy 1.2+ suppressor cells which are antigen-specific. These suppressor cells may be important in the regulation of CR-EAE and the techniques described for their generation may prove useful for treatment and prevention of disease.
慢性复发性实验性变应性脑脊髓炎（CR-EAE）可通过髓鞘碱性蛋白（BP）特异性辅助性T细胞系进行过继性转移，抑制性细胞可能在EAE的恢复中起重要作用。为了产生抑制性细胞，将从接种了BP-完全弗氏佐剂（CFA）的SJL/J小鼠和正常小鼠获得的脾细胞，分别与培养基、环孢素A（CsA）或CsA和抗原（BP或结核分枝杆菌纯化蛋白衍生物（PPD））一起培养7天。通过与源自SJL/J小鼠的BP特异性和PPD特异性辅助性T细胞系共培养，对培养的脾细胞进行体外抑制活性测定。用环孢素A（CsA）和BP培养的免疫供体脾细胞是T细胞系增殖的有效抑制剂，与对照脾细胞相比，抑制活性增加了17倍。将PPD特异性细胞系增殖抑制50%所需的抑制性细胞数量（I50）显著高于抑制BP特异性细胞系增殖所需的数量，提示抑制作用存在抗原特异性成分。抑制所需的主要效应细胞是具有巨噬细胞功能特征的大颗粒Mac-1+细胞。Thy 1.2+细胞耗竭后抑制活性仍然存在，但抑制作用不再具有抗原特异性，提示用CsA和BP培养脾细胞可能产生非抗原特异性的抑制性巨噬细胞和抗原特异性的Thy 1.2+抑制性细胞。这些抑制性细胞可能在CR-EAE的调节中起重要作用，所描述的产生它们的技术可能对疾病的治疗和预防有用。
