In vitro nucleoside specific immune response by lymphocytes from systemic lupus erythematosus

The in vitro immune response of systemic lupus erythematosus (SLE) lymphocytes to nucleosides conjugated to keyhole limpet hemocyanin (KLH) (A,G,C,T-KLH) was investigated. The nucleosides were chosen not only because they are a part of nucleic acid antigen and involved in autoimmunity, but also because nucleoside covalently bound to either soluble IgG or cells had been shown to induce unresponsiveness in mice. A significant proliferation index was induced in SLE lymphocytes, as compared with normal or rheumatoid arthritis (RA) lymphocytes in vitro [in (A,G,C,T)-KLH, 1 microgram/ml; stimulation index = M +/- SE, SLE 2.10 +/- 0.26, RA 1.06 +/- 0.14, normal 1.12 +/- 0.12 P less than 0.05]. Lymphocytes from SLE patients responded specifically to low doses of (A,G,C,T)-KLH and not to the protein carrier KLH alone. A solid-phase radioimmunoassay was developed to detect nucleoside-specific antibody. SLE lymphocytes spontaneously produced high levels of anti-A,G,C,T antibody. This was further increased by antigenic stimulation, but not with pokeweed mitogen (PWM) stimulation. In contrast normal lymphocytes failed to produce anti-A,G,C,T antibody either spontaneously or in response to antigen. However, normal lymphocytes produced antibody after stimulation with PWM. More importantly, anti-A,G,C,T antibody production by SLE lymphocytes was suppressed by preincubation with A,G,C,T-IgG (A,G,C,T-HGG). The antigen-specific unresponsiveness caused by A,G,C,T-HGG was demonstrated by the observation that preincubation with A,G,C,T-HGG did not affect the production of anti-dinitrophenyl antibody response. The ability to manipulate the altered response of SLE lymphocytes to nucleic acid antigens may have therapeutic implications in these patients.