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The forkhead family transcriptional factor (Foxp3) is an important lineage marker for regulatory T (Treg) cells. Foxp3 expression is primarily restricted to CD4+CD25+ cell population. Recently, an intriguing phenomenon is highlighted that there is a considerable amount of CD4(+)CD25(-)Foxp3(+) T cells present in the peripheral blood of patients with systemic lupus erythematosus (SLE). Up to now, it is still an open question as to the nature of this cell subset. Following an analyses of the available phenotypic characteristics of CD4(+)CD25(-)Foxp3(+) T cell subset along with some new findings in research of Treg in human SLE, we propose the hypothesis: the increased circulating CD4(+)CD25(-)Foxp3(+) T cells in patients with SLE may constitute a peripheral reservoir of CD4(+)CD25(+) Foxp3(+) Treg cells. Under the condition of autoimmune response reactivated, CD4(+)CD25(-)Foxp3(+) T cells could be recruited to expand the Treg pool upon CD25 regaining, for the effort to try to reverse a homeostatic imbalance shift to more aggressive expansion of autoreactive T cells and B cells. This hypothesis, if confirmed, would provide a new strategy for the treatment of SLE via the generation of therapeutic regulatory T cells.

The Nature of Increased Circulating CD4+CD25-Foxp3+ T Cells in Patients with Systemic Lupus Erythematosus: A Novel Hypothesis