Identity of mysterious CD4(+)CD25(-)Foxp3(+) cells in systemic lupus erythematosus

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(+)CD25(dim) 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.