Various abnormalities in CD4+CD25+ regulatory T cells (Tregs) in systemic lupus erythematosus (SLE) include increased Foxp3+ cells that are CD25 negative. Barring methodological technical factors, these cells could be atypical Tregs or activated non-Treg CD4+ cells that express Foxp3. Two groups have reached opposite conclusions that could possibly reflect the subjects studied. One group studied untreated new-onset SLE and suggested that these T cells were mostly CD25-Foxp3+ non-Tregs. The other group studied patients with long-standing disease and suggested that these cells are mostly dysfunctional Tregs. A third group reported increased Foxp3+CD4+CD25dim rather than CD25- cells in active SLE and these were also non-Tregs. Thus, it is likely that not all Foxp3+ T cells in SLE have protective suppressive activity.