Alteration of mitogenic responses of mononuclear cells by anti-ds DNA antibodies resembling immune disorders in patients with systemic lupus erythematosus.

Abstract

Anti-double-stranded DNA antibodies (anti-DNA) purified from pooled active SLE sera by lambda phage DNA-affinity chromatography was found to affect phytohemagglutinin (PHA) and pokeweek mitogen (PWM)-induced responses of normal mononuclear cells. Anti-DNA at a concentration of 0.25 mg/ml (equivalent to 21 units/ml of DNA binding activity) significantly suppressed the PHA-induced [3H]thymidine incorporation of mononuclear cells in 3 days of culture but had no effect on 5-day and 7-day cultures. In contrast, a biphasic effect of anti-DNA on PWM response was found such that early phase (3-day culture) was inhibited whereas late phase (from 5 days to 9 days of culture) was enhanced by the antibodies. Anti-DNA also increased the immunoglobulin synthesis by PWM-stimulated B cells. The inhibition of PHA response in 3-day culture by anti-DNA is not due to changes in T cell subpopulations. Because interleukin 1 (10 units/ml) could restore the PHA response, it appears that anti-DNA suppressed the IL-1 production by monocyte/macrophage. The biphasic effect of anti-DNA on PWM response is the result of monocyte impairment and B cell stimulation by the antibodies. In the early phase (on day 3) the inhibition would seem to be due to impairment of accessory cell function by anti-DNA, though in late phase (after day 5) the anti-DNA may stimulate B lymphocytes to incorporate more thymidine in the presence of PWM. These biological effects of anti-DNA in vitro resemble the in vivo immunologic disorders in patients with SLE, in that impaired cell-mediated immunity and B cell hyperactivity are frequently observed.