Jung S, Toyka K, Hartung H P
Department of Neurology, Julius-Maximilians-Universität Würzburg, Germany.
Eur J Immunol. 1995 May;25(5):1391-8. doi: 10.1002/eji.1830250538.
The immunotherapeutic potential of three anti-rat CD2 monoclonal antibodies (mAb) (OX34, OX54, OX55) and the combination of OX54 with OX55 was tested in Lewis rat experimental autoimmune encephalomyelitis (EAE). In actively induced EAE, a single injection of OX34 2 days before immunization with myelin basic protein (MBP) in complete Freund's adjuvant (CFA) completely prevented or greatly attenuated EAE in all animals. Injection of OX54 acted moderately suppressive while OX55 or OX54/55 did not affect disease severity. Abrogation of EAE by OX34 was not restricted to its application before immunization. Therapeutic administration of all three mAb and the Ab combination from onset of first clinical signs efficiently blocked progression of disease and prevented all animals from developing hind limb paresis. In adoptive transfer EAE induced with in vitro activated cells of an encephalitogenic T helper line, clinical and histological signs were completely prevented by injection of OX34 on the day of cell transfer and 4 days later, underlining the strong impact of anti-CD2 mAb on the effector phase of disease. Immunocytofluorometric analysis of peripheral blood lymphocytes after a single Ab injection demonstrated that all mAb induced a variable degree of transient reduction in T cell numbers and modulation of CD2 antigens. In contrast to the other mAb, OX34 persisted on lymphocytes for at least 11 days, which may explain its unique suppressive effect on EAE after a single injection before immunization. The assumption that prophylactic administration of OX34 also inhibits MBP-induced EAE, due to persistence into the effector phase, was substantiated by the finding that none of the mAb prevented generation of an antigen-specific cellular response in MBP/CFA-immunized animals. Since none of the Ab induced T cell unresponsiveness or inhibited T cell activation by antigen- or Ab-mediated stimulation of the T cell receptor, we suggest that their marked action on the effector phase of EAE may rely on inhibition of T cell infiltration into the central nervous system. The demonstrated efficacy of these anti-CD2 mAb in EAE suggests a potential therapeutic role that may be equal to that of anti-CD4 or anti-T cell receptor Ab.
在Lewis大鼠实验性自身免疫性脑脊髓炎（EAE）中测试了三种抗大鼠CD2单克隆抗体（mAb）（OX34、OX54、OX55）以及OX54与OX55联合使用的免疫治疗潜力。在主动诱导的EAE中，在完全弗氏佐剂（CFA）中用髓鞘碱性蛋白（MBP）免疫前2天单次注射OX34可完全预防或显著减轻所有动物的EAE。注射OX54有中度抑制作用，而OX55或OX54/55不影响疾病严重程度。OX34对EAE的消除并不局限于免疫前应用。从首次出现临床症状开始，对所有三种mAb和抗体组合进行治疗性给药可有效阻断疾病进展，并防止所有动物出现后肢麻痹。在用致脑炎性T辅助细胞系的体外活化细胞诱导的过继转移EAE中，在细胞转移当天和4天后注射OX34可完全预防临床和组织学症状，这突出了抗CD2 mAb对疾病效应期的强烈影响。单次注射抗体后对外周血淋巴细胞进行免疫细胞荧光分析表明，所有mAb均诱导T细胞数量出现不同程度的短暂减少以及CD2抗原的调节。与其他mAb不同，OX34在淋巴细胞上持续存在至少11天，这可能解释了其在免疫前单次注射后对EAE具有独特的抑制作用。由于持续至效应期，OX34预防性给药也抑制MBP诱导的EAE这一假设得到了以下发现的证实：在MBP/CFA免疫的动物中，没有一种mAb能阻止抗原特异性细胞反应的产生。由于没有一种抗体诱导T细胞无反应性或通过抗原或抗体介导的T细胞受体刺激抑制T细胞活化，我们认为它们对EAE效应期的显著作用可能依赖于抑制T细胞浸润到中枢神经系统。这些抗CD2 mAb在EAE中显示出的疗效表明其潜在治疗作用可能与抗CD4或抗T细胞受体抗体相当。
