Treg defects in patients with SLE are associated with IL-2 deficiency, and can be corrected with low doses of IL-2. The restoration of endogenous mechanisms of immune tolerance by low-dose IL-2 therapy, thus, proposes a selective biological treatment strategy, which directly addresses the pathophysiology in SLE.

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Systemic lupus erythematosus is a systemic and chronic autoimmune disease characterized by loss of tolerance towards nuclear antigens with autoreactive CD4 D T cells implicated in disease pathogenesis. However, very little is known about their receptor specificity since the detection of human autoantigen specific CD4 D T cells has been extremely challenging. Here we present an analysis of CD4 D T cells reactive to nuclear antigens using two complementary methods: T cell libraries and antigenreactive T cell enrichment. The frequencies of nuclear antigen specific CD4 D T cells correlated with disease severity. These autoreactive T cells produce effector cytokines such as interferon-g, interleukin-17, and interleukin-10. Compared to blood, these cells were enriched in the urine of patients with active lupus nephritis, suggesting an infiltration of the inflamed kidneys. Thus, these previously unrecognized characteristics support a role for nuclear antigen-specific CD4 D T cells in systemic lupus erythematosus.