Demonstration of impaired T cell regulation of Epstein-Barr virus stimulated B lymphoyctes in rheumatoid arthritis with HLA identical, disease discordant sibling pairs

Abstract

Lymphocytes from patients with rheumatoid arthritis (RA) show an abnormal response after stimulation with Epstein-Barr virus (EBV), a potent B cell mitogen. In vitro IgM production from EBV stimulated lymphocytes was measured over a 21 day period. In keeping with previous studies, RA lymphocytes showed increasing IgM production between 14 and 21 days, whereas IgM production decreased during this period in normal lymphocytes (p < 0.001). Experiments on 12 HLA identical, RA discordant sibling pairs were also undertaken. B enriched and T enriched lymphocyte populations were obtained and recombined in both an autologous and homologous manner. The abnormality in IgM production in patients with RA was shown to reside in the RA T cell population (p < 0.005), and RA B cells combined with normal T cells behaved similarly to autologous cultures of normal B and T cells. The study shows that impaired immunoregulation of EBV stimulated B cells in RA is secondary to a functional defect in RA T cells, but no difference in the concentration of T suppressor/cytotoxic cells could be found between the disease discordant siblings. The abnormality in immunoregulation appears to be secondary to RA, rather than a product of genes encoded within the major histocompatibility complex (MHC) region, as defined by HLA-DR, A, B, and C typing.