Lysis of autologous Epstein-Barr virus-infected B cells by cytotoxic T lymphocytes of rheumatoid arthritis patients

Since B lymphocytes of patients with rheumatoid arthritis (RA) have a higher rate of Epstein-Barr virus (EBV)-induced transformation than normal B cells, we have investigated whether this phenomenon is related to defective cytotoxic T-cell control of emerging B-cell clones. We have studied the in vitro generation of cytotoxic T lymphocytes specific for antigens appearing on autologous B cells after EBV infection using lymphocytes from six patients with RA. Cytotoxic cells were generated by two cycles of stimulation with mitomycin C-treated autologous B cells, and their lytic activity was assessed against 51Cr-labeled targets. As previously reported for lymphocytes of normal individuals, RA cytolytic T lymphocytes were induced only by EBV-infected B cells, not by noninfected B cells, and expression of the cytotoxicity required EBV-transformed targets. After primary in vitro stimulation with autologous EBV-infected B cells, the RA cytotoxic cells expressed higher lytic activity than the normal counterparts, but the difference was not statistically significant (P > 0.1). However, after secondary in vitro stimulation both groups displayed similar cytotoxic activities. In the presence of complement, monoclonal antibodies OKT8 (characterizing cytotoxic/suppressor cells), SC1, and OKT3 (characterizing most T cells) reduced cytotoxicity by 80–90%; antibody OKT3 also reduced the lytic activity by 68% in the absence of complement. We conclude that the higher EBV-induced transformation rate seen with RA lymphocytes is not explained by a deficiency in this EBV-specific cytotoxic T cell.