Goldschmidt T J, Holmdahl R
Department of Medical and Physiological Chemistry, Uppsala University, Sweden.
Cell Immunol. 1994 Mar;154(1):240-8. doi: 10.1006/cimm.1994.1072.
The role which T cells play in the pathogenesis of the collagen-induced arthritis (CIA) model is not yet fully understood. Although CIA is most likely dependent on the activity of class II-restricted CD4+ T cells, only prophylactic but not therapeutic anti-CD4 treatments have been successful. The lack of therapeutically effective anti-T cell monoclonal antibody treatments has questioned the importance of T cells in ongoing CIA. However, recently we found that ongoing CIA in DA rats induced with homologous CII can be suppressed by injections with an anti-alpha beta TCR antibody. Having a CIA model where ongoing disease was clearly dependent on T cells, we addressed in the present work whether also an anti-CD4 treatment could suppress ongoing arthritis in this model. Although no CD4hi lymph node cells were seen after an anti-CD4 injection, the arthritis was suppressed only after treatment at immunization but not after treatment just before onset of disease. In comparison, the anti-TCR treatment at the time of onset was clearly suppressive even though a large fraction of the T cells was not depleted. This indicates that the different outcome of the anti-TCR and anti-CD4 treatment was not due to a different capacity to deplete T cells in vivo.
T细胞在胶原诱导性关节炎（CIA）模型发病机制中所起的作用尚未完全明确。尽管CIA很可能依赖于Ⅱ类分子限制性CD4⁺T细胞的活性，但只有预防性而非治疗性的抗CD4治疗取得了成功。缺乏具有治疗效果的抗T细胞单克隆抗体治疗引发了对T细胞在持续性CIA中重要性的质疑。然而，最近我们发现，用抗αβTCR抗体注射可抑制用同源Ⅱ型胶原诱导的DA大鼠的持续性CIA。由于有了一个疾病进展明显依赖于T细胞的CIA模型，我们在当前研究中探讨了抗CD4治疗是否也能抑制该模型中的持续性关节炎。尽管注射抗CD4后未见CD4⁺高表达的淋巴结细胞，但关节炎仅在免疫时治疗后得到抑制，而在疾病即将发作前治疗则无效。相比之下，发病时的抗TCR治疗即使在大部分T细胞未被清除的情况下仍具有明显的抑制作用。这表明抗TCR和抗CD4治疗结果不同并非由于体内清除T细胞的能力不同。
