Natural regulatory T cells: number and function are normal in the majority of patients with lupus nephritis

CD4(+) CD25(+) regulatory T cells have been shown to be a vital component of the mechanisms that prevent autoreactivity in mice and also in humans. Previous studies have examined CD4(+) CD25(hi) regulatory T cell frequency and function in patients with systemic lupus erythematosus (SLE) with mixed results. We investigated frequency, phenotype and function in 21 patients with SLE and six with inactive disease. We found no reduction in frequency of the CD25(hi) subset, although active disease was associated with an increased proportion of CD4(+) CD25(+) T cells. When examining function, in the majority of individuals suppression was comparable with controls, although cells isolated from one patient with active disease failed to suppress proliferation. On testing the effect of CD25(hi) depletion on the responses of whole peripheral blood mononuclear cells to nucleosomes we found that, where a response was detectable from patients, depletion augmented interferon-gamma secretion, demonstrating intact suppression of responses implicated in the pathogenesis of SLE. Our results did not confirm an association of failure in CD4(+) CD25(hi) regulatory T cell function or a reduction in their frequency with active disease. Instead, perturbations in the CD4(+) CD25(hi) regulatory T cell population may play a role in disease in only a minority of the patients afflicted by the diverse syndromes of SLE.