Reactive arthritis after BCG immunotherapy: T cell analysis in peripheral blood and synovial fluid

Abstract

Objective. 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. Methods. 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. Results. 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. Conclusion. 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.