Bartolome Pacheco M J, Martinez-Taboada V M, Blanco R, Rodriguez-Valverde V, Valle J I, Lopez-Hoyos M
Division of Immunology, Hospital Universitario Marqués de Valdecilla, Facultad de Medicina, Universidad de Cantabria, Santander, Spain.
Rheumatology (Oxford). 2002 Oct;41(10):1119-25. doi: 10.1093/rheumatology/41.10.1119.
To investigate the pathogenic mechanism of reactive arthritis after instillation of Calmette-Guérin bacillus (BCG). Although the clinical features of reactive arthritis after BCG therapy are well described, only a few reports have studied the possible pathogenic mechanisms.
We analysed by flow cytometry the phenotype and T-cell receptor (TCR) expression of peripheral blood (PB) and synovial fluid (SF) T cells in a patient who developed reactive arthritis (ReA) following intravesical BCG immunotherapy for bladder cancer. The proliferative response of short-term T-cell lines (TCL) from PB of this patient to mycobacterial antigens was tested by bromodeoxyuridine incorporation.
CD4(+) and CD8(+) SF T cells with activated and memory phenotype were observed at the onset of arthritis. We were able to detect BV-restricted expansion of CD8(+) T cells in PB (BV17) and in SF (BV5S1 and BV12). The percentage of PB and SF CD8(+) T cells that expanded diminished when the symptoms remitted. The strongest response of CD4(+) TCL from the patient in vitro was obtained for human hsp-60 in an inversely dose-dependent manner. Very important was the finding that CD8(+) TCL from the patient demonstrated no proliferative response to any antigenic challenge that was reversed after the addition of exogenous interleukin 2.
Although the identity of the stimulating antigen that led to the expansions observed in this patient is not clarified by the present data, both CD4(+) and CD8(+) T cells might play a role in the development of ReA following intravesical administration of BCG.
研究卡介苗(BCG)灌注后反应性关节炎的发病机制。尽管BCG治疗后反应性关节炎的临床特征已有详尽描述,但仅有少数报告研究了可能的发病机制。
我们通过流式细胞术分析了一名膀胱癌患者在膀胱内BCG免疫治疗后发生反应性关节炎(ReA)时外周血(PB)和滑液(SF)T细胞的表型及T细胞受体(TCR)表达。通过溴脱氧尿苷掺入法检测了该患者PB来源的短期T细胞系(TCL)对分枝杆菌抗原的增殖反应。
在关节炎发作时观察到具有活化和记忆表型的CD4(+)和CD8(+) SF T细胞。我们能够检测到PB中(BV17)和SF中(BV5S1和BV12)CD8(+) T细胞的BV限制性扩增。症状缓解时,PB和SF中扩增的CD8(+) T细胞百分比降低。该患者的CD4(+) TCL在体外对人热休克蛋白60(hsp-60)的反应最强,呈反向剂量依赖性。非常重要的是,该患者的CD8(+) TCL对任何抗原刺激均无增殖反应,但添加外源性白细胞介素2后这种反应得到逆转。
尽管目前的数据尚未明确导致该患者观察到的扩增的刺激抗原的身份,但CD4(+)和CD8(+) T细胞可能在膀胱内给予BCG后ReA的发生中起作用。