Svelander L, Müssener A, Erlandsson-Harris H, Kleinau S
Department of Rheumatology, Karolinska Hospital, Stockholm, Sweden.
Immunology. 1997 Jun;91(2):260-5. doi: 10.1046/j.1365-2567.1997.00251.x.
T-cells play a critical role in oil-induced arthritis (OIA) in DA rats. The present study focuses on the involvement of CD4/CD8 T cells in OIA by using adoptive transfer. Mitogen-activated T cells from DA rats previously injected with incomplete Freund's adjuvant (IFA) were depleted of CD4+ T cells or CD8+ T cells before transfer to irradiated naive receipients. The results indicate that CD4+ T cells are essential for the induction of passively induced OIA. However, in vitro blocking experiments with monoclonal antibodies (mAb) to the CD4 molecule of the T cells before transfer did not affect the passive OIA. Neither was passive OIA inhibited by treating the CD4+ T cells with mAb to intracellular adhesion molecule-1 (ICAM-1) in order to block cell-cell interactions or migration. The arthritogenic CD4+ T cells were sensitive, however, to in vitro treatment with mAb to the interleukin-2 receptor, which inhibited the disease or delayed the onset of passive OIA in recipients. The arthritogenic CD4+ T cells were also analysed for expression of specific T-cell receptor (TCR) variable (V) beta chains, critical for recognition of autoantigen, by utilizing V beta gene-specific polymerase chain reaction (PCR). The results show a heterogeneous expression of V beta segments of the TCR, indicating a polyclonal origin of the pathogenic cells. Moreover, an investigation of the T helper (Th)1/Th2 status of the CD4+ T cells, defined by cytokine expression, was made at the mRNA level by using in situ hybridization. High numbers of interleukin-2 (IL-2) mRNA expressing cells and also interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha)-expressing cells could be identified. We conclude from this study that non-immunogenic IFA triggers polyclonal, IL-2-dependent Th1 cells which induce arthritis. The contribution of the CD4 or ICAM-1 molecules for arthritis induction seem to be of minor importance.
T细胞在DA大鼠的油诱导性关节炎（OIA）中起关键作用。本研究通过采用过继转移，着重探讨CD4/CD8 T细胞在OIA中的作用。将先前注射不完全弗氏佐剂（IFA）的DA大鼠经丝裂原激活的T细胞，在转移至经照射的未致敏受体之前，去除CD4⁺ T细胞或CD8⁺ T细胞。结果表明，CD4⁺ T细胞对于被动诱导的OIA的诱导至关重要。然而，在转移前用针对T细胞CD4分子的单克隆抗体（mAb）进行体外阻断实验，并不影响被动性OIA。用针对细胞间黏附分子-1（ICAM-1）的mAb处理CD4⁺ T细胞以阻断细胞间相互作用或迁移，也不会抑制被动性OIA。然而，致关节炎的CD4⁺ T细胞对用针对白细胞介素-2受体的mAb进行体外处理敏感，这会抑制疾病或延迟受体中被动性OIA的发作。还通过利用Vβ基因特异性聚合酶链反应（PCR）分析致关节炎的CD4⁺ T细胞中对自身抗原识别至关重要的特异性T细胞受体（TCR）可变（V）β链的表达。结果显示TCR的Vβ片段表达具有异质性，表明致病细胞起源于多克隆。此外，通过原位杂交在mRNA水平上对由细胞因子表达定义的CD4⁺ T细胞的辅助性T细胞（Th）1/Th2状态进行了研究。可以鉴定出大量表达白细胞介素-2（IL-2）mRNA的细胞，以及表达干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）的细胞。我们从这项研究得出结论，非免疫原性的IFA触发多克隆、IL-2依赖性的Th1细胞，这些细胞诱导关节炎。CD4或ICAM-1分子对关节炎诱导的作用似乎不太重要。
