Phenotypic and functional similarities between 5-azacytidine-treated T cells and a T cell subset in patients with active systemic lupus erythematosus.

OBJECTIVE: Antigen-specific CD4+ T cells treated with DNA methylation inhibitors become autoreactive, suggesting a novel mechanism for autoimmunity. To test whether this mechanism might be involved in systemic lupus erythematosus (SLE), phenotypic markers for the autoreactive cells were sought. METHODS: Cloned normal T cells were treated with the DNA methylation inhibitor 5-azacytidine (5-azaC) and studied for altered gene expression. T cells from patients with active SLE were then studied for a similar change in gene expression, and cells expressing the marker were tested for autoreactivity. RESULTS: 5-azaC-treated normal T cells had increased CD11a (leukocyte function-associated antigen 1 alpha) expression relative to other membrane molecules. A T cell subset with similar CD11a expression was found in patients with active SLE. This subset contained cells that spontaneously lysed autologous macrophages, with a specificity similar to that of 5-azaC-treated cells.

Immunosuppressive drug therapy for rheumatic disease.

The use and complications of intravenous cyclophosphamide, azathioprine, nitrogen mustard, and cyclosporine are reviewed. Studies have failed to demonstrate superiority of intravenous versus oral cyclophosphamide in rheumatic diseases other than systemic lupus. Azathioprine is a useful immunosuppressive agent in Beçhet's disease. Further studies of cyclosporine in rheumatoid arthritis indicate that efficacy and toxicity are both dose related.