Autoantibody to an Immunoregulatory Inducer Population in Patients with Juvenile Rheumatoid Arthritis

Abstract

The human inducer (T4⁺) and reciprocal cytotoxic/suppressor (T5⁺/T8⁺) subsets have been defined by monoclonal antibodies. In the present study, we examined the relationship of naturally occurring anti-T cell autoantibodies found in patients with active juvenile rheumatoid arthritis (JRA) to these subsets. In one approach, normal T cells were treated with anti-T4 or anti-T8 to eliminate the corresponding subset of cells and then analyzed for reactivity with JRA sera. It was found that JRA sera were reactive with only 15% of an enriched cytotoxic/suppressor population, whereas they reacted with 37% of an enriched inducer population. In reciprocal studies, JRA⁺ T cells were eliminated with JRA sera and complement and the residual T cells (JRA⁻) reacted with monoclonal antibodies and indirect immunofluorescence on a fluorescence-activated cell sorter. As expected, the JRA sera and complement treatment of unfractionated T cells markedly diminished the T4⁺ subset, whereas there was a concomitant increase in T cells reactive with anti-T5 and anti-T8. A similar diminution in T4⁺ T cells was found in the circulating peripheral T cell compartment of patients with active JRA who possessed the JRA antibody. Functional studies demonstrated that removal of the JRA⁺ population of T cells diminished phytohemagglutinin and soluble antigen proliferative responses, both of which were previously shown to be functions of T4⁺ T cells. More importantly, in the absence of JRA⁺ T cells, pokeweed mitogen-stimulated immunoglobulin production was markedly enhanced, despite the concomitant increase in T5⁺/T8⁺ cytotoxic/suppressor cells. These results suggest that the JRA serum may define a Qal-like antigen found predominantly on the human inducer population which could activate suppressor and/or other feedback regulatory cells.