Counter-proliferative effects of nucleosomal antigens in cultures from lupus patients

Blood mononuclear cells from 20 lupus patients were cultured in the presenc e of nucleosomal antigens to determine whether they induce lymphocyte proli feration. The predominant effect seen, however, was one of inhibition of th e background proliferation. Such inhibition was rare with cells from female or male controls. Nucleohistone (NH), crude histone and enriched preparati ons of histones H2A/H4, H2B and H3 showed this effect in approximately one- third of patients, but H1 and single-stranded (ss) DNA had no such activity . Double-stranded (ds) DNA may show this inhibitory action, but further tes ts are required. ssDNA was the only antigen that showed evidence (two patie nts) of disease-related stimulation of proliferation. Histones and NH induc ed proliferation in many subjects but the strongest responders were control s. Patients responded poorly to tuberculin PPD but gave an exceptionally st rong proliferative response to pokeweed mitogen. It is suggested that the i nhibition of background proliferation in patients is a consequence of the i nteraction of nucleosomal antigens with sensitised T cells. If T cell sensi tisation to histones is an important factor in the development of lupus, th e disease may be preventable in those at risk by inducing tolerance to the appropriate peptides.