Drug-induced autoantibody formation in mice: triggering by primed CD4+CD25- T cells, prevention by primed CD4+CD25+ T cells.

Although the ability of CD4+CD25+ T suppressor (Ts) cells to prevent experimental autoimmune diseases has been described, nothing is known concerning their role and mechanism of action in xenobiotic-induced autoimmunity. Procainamide, mercuric chloride, and gold(I) are three xenobiotics that can induce autoimmune reactions in humans and rodents. After the induction of IgG1 antinuclear autoantibodies (ANA) in mice treated with either of the above xenobiotics, adoptive transfer of their CD4+CD25+ T cells completely prevented ANA formation in recipients treated with the same xenobiotic; transfer of CD8+ T cells was ineffective. Furthermore, xenobiotic-primed CD4+CD25+ T cells could also partially prevent ANA formation in recipients treated with a different xenobiotic. CD4+CD25- T cells from xenobiotic-treated donors failed to suppress, but induced de novo IgG1 ANA formation in untreated recipients. Our findings suggest that during xenobiotic treatment T cell reactivity may spread from xenobiotic-induced, nucleoprotein-related neoantigens to peptides of the unaltered nucleoproteins.