Hoffmann J C, Herklotz C, Zeidler H, Bayer B, Westermann J
Abteilung Rheumatologie, Zentrum Innere Medizin und Dermatologie, Medizinische Hochschule Hannover, Germany.
Clin Exp Immunol. 1997 Oct;110(1):63-71. doi: 10.1046/j.1365-2249.1997.4881385.x.
Anti-CD2 MoAbs have previously been shown to induce tolerance and to block B cell differentiation, T cell and monocyte activation. Since these immune functions are important in joint inflammation, we asked whether administration of the anti-CD2 MoAb OX34 has a beneficial effect on established rat adjuvant arthritis, a model of human rheumatoid arthritis, and how it affects CD2-bearing leucocyte subsets. Female Lewis rats with established adjuvant arthritis received a total of 5 mg OX34 or isotype-matched control MoAb starting on day 15 after adjuvant injection. Weight and arthritis score (AS) were measured in a blinded fashion. Peripheral blood cells were analysed for numbers of leucocyte subsets at various time points. Animals were killed on day 30 and lymphatic organs were processed for immunohistology. Clinically, OX34 treatment led to increased body weight and reduced AS. Although OX34 binds to CD4+ and CD8+ T cells in a comparable fashion, OX34 treatment reduced CD4+ T cells, but not CD8+ T cells. Among CD4+ T cells CD45RC+ ('naive') T cells virtually disappeared; CD45RC- ('recently activated') T cells were slightly reduced. A reduction of CD4+ T cells was also found in the lung, liver, bone marrow, spleen and lymph nodes. Down-modulation of the CD2 molecule by OX34, again, affected CD4+ T cells, suggesting a specific signal for CD4+ but not CD8+ T cells. In conclusion, the anti-CD2 MoAb OX34 attenuates established rat adjuvant arthritis. In spite of similar binding to CD4+ and CD8+ T cells, OX34 depletes only CD4+ T cells and down-modulates the CD2 molecule on these cells. These results suggest a therapeutic benefit from CD2-directed therapy for chronic types of arthritis.
先前已证明抗CD2单克隆抗体可诱导免疫耐受，并阻断B细胞分化、T细胞和单核细胞活化。由于这些免疫功能在关节炎症中很重要，我们探讨了给予抗CD2单克隆抗体OX34对已建立的大鼠佐剂性关节炎（一种人类类风湿性关节炎模型）是否具有有益作用，以及它如何影响表达CD2的白细胞亚群。在佐剂注射后第15天开始，给患有已建立佐剂性关节炎的雌性Lewis大鼠总共注射5mg OX34或同型对照单克隆抗体。以盲法测量体重和关节炎评分（AS）。在不同时间点分析外周血细胞中白细胞亚群的数量。在第30天处死动物，并对淋巴器官进行免疫组织学处理。临床上，OX34治疗导致体重增加和AS降低。尽管OX34以类似方式与CD4 +和CD8 + T细胞结合，但OX34治疗减少了CD4 + T细胞，而未减少CD8 + T细胞。在CD4 + T细胞中，CD45RC +（“幼稚”）T细胞几乎消失；CD45RC -（“最近活化”）T细胞略有减少。在肺、肝、骨髓、脾脏和淋巴结中也发现CD4 + T细胞减少。OX34对CD2分子的下调再次影响了CD4 + T细胞，表明这是CD4 +而非CD8 + T细胞的特异性信号。总之，抗CD2单克隆抗体OX34减轻了已建立的大鼠佐剂性关节炎。尽管与CD4 +和CD8 + T细胞有类似结合，但OX34仅消耗CD4 + T细胞并下调这些细胞上的CD2分子。这些结果表明针对慢性关节炎的CD2导向治疗具有治疗益处。
