Impaired regulation of Epstein-Barr virus-induced lymphocyte proliferation in rheumatoid arthritis is due to a T cell defect.
The rate of outgrowth of EBV-infected B lymphocytes is regulated by normal T lymphocytes. Removal of T cells from normal whole lymphoid populations (PBM) markedly shortens the outgrowth time of the remaining B lymphocytes. There is little difference in the much more rapid outgrowth of rheumatoid PBM after the removal of T cells, which suggests that RA lymphoid cells are unable to regulate this process. To determine whether RA T cells are defective, or EBV-infected RA B cells are unresponsive to regulatory signals, EBV-induced outgrowth in autologous and allogeneic mixtures of RA and normal B and T cells was evaluated, employing morphologic criteria and 3H-thymidine incorporation. The difference in outgrowth between RA and normal PBM was reproduced by reconstitution of EBV-infected B cells with mitomycin-treated autologous T cells. In cell-mixing experiments, normal T cells appropriately regulated both normal and RA B cells similarly, whereas RA T cells were defective in regulating either B cell population. Thus, the rapid outgrowth of EBV-infected rheumatoid lymphoid cells is due to defective T cell regulation. Moreover, normal regulation does not require cell proliferation.
D000914:Antibodies, Viral / Q000096:biosynthesis; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D004247:DNA / Q000096:biosynthesis; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology*
D000914:Antibodies, Viral; D004247:DNA