Phenotypic and functional similarities between 5‐azacytidine‐treated t cells and a t cell subset in patients with active systemic lupus erythematosus

Abstract

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 1α) 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. Conclusion. The model of 5‐azaC‐induced autoreactivity may have relevance to SLE.