Popov I, Dela Cruz C S, Barber B H, Chiu B, Inman R D
Division of Rheumatology, Department of Medicine, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
J Immunol. 2001 Sep 15;167(6):3375-82. doi: 10.4049/jimmunol.167.6.3375.
The interplay between triggering bacteria and HLA-B27 in the pathogenesis of the spondyloarthropathies remains one of the most active areas of investigation in the rheumatic diseases. This has proved difficult to study systematically in the clinical setting, and in this study we utilized a rat model to address the influence that B27-related immunity may have on the process of generating anti-Chlamydia immunity. When splenocytes from HLA-B27 DNA-immunized Lewis (LEW) animals received restimulation in vitro with Chlamydia-treated cells from B27-transgenic LEW rats, we observed that in addition to the expected CTL recognition of HLA-B27, there was also anti-Chlamydia CTL killing of Chlamydia-sensitized syngeneic fibroblast targets. This was not seen when responding cells in vitro were naive LEW splenocytes. To confirm the existence of CTLs recognizing both HLA-B27 and Chlamydia, LEW rats were immunized with B27-transgenic LEW cells, instead of the B27 DNA construct. Splenocytes from the immune rats were restimulated in vitro with Chlamydia-treated B27-transgenic LEW cells. In this instance, the CTLs retained the allele-specific recognition of HLA-B27, as well as recognition of Chlamydia-sensitized syngeneic fibroblasts. Thus, if there is prior expansion of an immune response against HLA-B27, then the resulting splenocytes demonstrate a reduced threshold for generating a primary anti-Chlamydia CTL response. These studies implicate a dynamic interrelationship between recognition of HLA-B27 and Chlamydia trachomatis. The results may have implications for deciphering the cellular basis of Chlamydia-induced reactive arthritis.
在脊柱关节病发病机制中，触发细菌与HLA - B27之间的相互作用仍是风湿病研究中最活跃的领域之一。事实证明，在临床环境中对其进行系统研究很困难，在本研究中，我们利用大鼠模型来探讨B27相关免疫可能对产生抗衣原体免疫过程产生的影响。当用衣原体处理的B27转基因LEW大鼠的细胞在体外对来自经HLA - B27 DNA免疫的Lewis（LEW）动物的脾细胞进行再刺激时，我们观察到，除了预期的HLA - B27特异性CTL识别外，还存在对衣原体致敏的同基因成纤维细胞靶标的抗衣原体CTL杀伤作用。当体外反应细胞为未经免疫的LEW脾细胞时，未观察到这种现象。为了证实同时识别HLA - B27和衣原体的CTL的存在，用B27转基因LEW细胞而非B27 DNA构建体免疫LEW大鼠。用衣原体处理的B27转基因LEW细胞在体外对免疫大鼠的脾细胞进行再刺激。在这种情况下，CTL保留了对HLA - B27的等位基因特异性识别，以及对衣原体致敏的同基因成纤维细胞的识别。因此，如果先前存在针对HLA - B27的免疫反应扩增，那么产生的脾细胞在产生原发性抗衣原体CTL反应时表现出降低的阈值。这些研究表明HLA - B27和沙眼衣原体的识别之间存在动态相互关系。该结果可能对解读衣原体诱导的反应性关节炎的细胞基础具有启示意义。
