OVEREXPRESSION AND T CELL AUTOREACTIVITY

Objective. To determine if DNA methylation in-hibitors make T cells autoreactive by inducing lympho-cyte function-associated antigen type 1 (LFA-1) ( C D l l d CD18) overexpression. Methods. T cell clones were treated with 3 dis-tinct DNA methylation inhibitors or were stably trans-fected with a CD18 cDNA in a mammalian expression vector, and the effects on LFA-1 expression and activa-tion requirements were examined. Results. LFA-1 overexpression, caused by DNA methylation inhibitors or by transfection, correlates with the development of autoreactivity. Conclusion. LFA-1 overexpression may contrib-ute to T cell autoreactivity. Investigators at this laboratory have reported that human and murine cloned, antigen-specific, CD4+ T cells become autoreactive following treatment with DNA methylation inhibitors like 5-azacytidine (5-azaC) and procainamide (PCA) (1-3). The autoreac-tivity has pathologic significance, because T cells made autoreactive with these drugs are sufficient to cause a lupus-like disease when injected into syngeneic mice (3). This system is relevant to human lupus, because PCA induces a lupus-like disease in patients receiving this drug (4), and because patients with idiopathic lupus hav