Kraft M, Filsinger S, Krämer K L, Kabelitz D, Hänsch G M, Schoels M
Institute of Immunology, University of Heidelberg, Germany.
Immunology. 1998 Jan;93(1):20-5. doi: 10.1046/j.1365-2567.1998.00398.x.
Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown aetiology. Recently, superantigens have been implied in the pathogenesis of RA. Superantigens activate a large fraction of T cells leading to the production of cytokines and proliferation. In addition, superantigens direct cellular cytotoxicity towards major histocompatibility complex (MHC) class II-expressing cells. There is now increasing evidence that cytotoxic T cells may be involved in the pathogenesis of RA. In the inflamed synovia class II-positive synovial fibroblasts (SFC) are found. In the present study it was tested whether MHC class II-positive SFC serve as target cells for superantigen-induced cellular cytotoxicity. SFC were stimulated with interferon-gamma to express class II antigens, then they were cultivated in the presence of CD4-positive T cells with or without staphylococcal enterotoxins (SE). Cytotoxicity of T cells was measured as release of lactate dehydrogenase from SFC. Specific cytotoxicity was only found in the presence of class II-positive SFC depending on the dose of SE. Maximum lysis was seen after 20 hr. T-cell cytotoxicity was inhibited by antibodies to MHC class II antigens. The data suggest that class II-positive SFC not only function as accessory cells for SE-mediated T-cell proliferation and interleukin-2 production but may also be the targets of superantigen-mediated cellular cytotoxicity.
类风湿关节炎（RA）是一种病因不明的慢性自身免疫性疾病。最近，超抗原被认为与RA的发病机制有关。超抗原可激活大部分T细胞，导致细胞因子的产生和细胞增殖。此外，超抗原可直接对表达主要组织相容性复合体（MHC）Ⅱ类分子的细胞产生细胞毒性作用。现在越来越多的证据表明，细胞毒性T细胞可能参与了RA的发病机制。在炎症性滑膜中可发现Ⅱ类阳性滑膜成纤维细胞（SFC）。在本研究中，检测了MHCⅡ类阳性SFC是否作为超抗原诱导的细胞毒性作用的靶细胞。用γ干扰素刺激SFC以表达Ⅱ类抗原，然后将其在有或无葡萄球菌肠毒素（SE）存在的情况下与CD4阳性T细胞一起培养。通过检测SFC中乳酸脱氢酶的释放来测定T细胞的细胞毒性。仅在存在Ⅱ类阳性SFC且依赖于SE剂量的情况下发现特异性细胞毒性。20小时后可见最大细胞裂解。MHCⅡ类抗原抗体可抑制T细胞的细胞毒性。这些数据表明，Ⅱ类阳性SFC不仅作为SE介导的T细胞增殖和白细胞介素-2产生的辅助细胞发挥作用，而且可能也是超抗原介导的细胞毒性作用的靶细胞。
