CD4⁺CD25⁻Foxp3⁺ T cells: a marker for lupus nephritis?

Systemic lupus erythematosus (SLE) is a heterogenous autoimmune disease, which can affect different organs. Increased proportions of CD4⁺CD25-Foxp3⁺ T cells have been described in SLE patients. The exact role of this cell population in SLE patients still remains unclear. We therefore analyzed this T cell subset in a large cohort of SLE patients with different organ manifestations.

Phenotypic analyses, proportions and absolute cell numbers of CD4⁺CD25-Foxp3⁺ T cells were determined by flow cytometry (FACS) in healthy controls (HC) (n = 36) and SLE patients (n = 61) with different organ manifestations. CD4⁺CD25⁻Foxp3⁺ T cells were correlated with clinical data, the immunosuppressive therapy and different disease activity indices. In patients with active glomerulonephritis, CD4⁺CD25⁻Foxp3⁺ T cells were analyzed in urine sediment samples. Time course analyses of CD4⁺CD25⁻Foxp3⁺ T cells were performed in patients with active disease activity before and after treatment with cyclophosphamide and prednisone.

CD4⁺CD25⁻Foxp3⁺ T cells were significantly increased in active SLE patients and the majority expressed Helios. Detailed analysis of this patient cohort revealed increased proportions of CD4⁺CD25⁻Foxp3⁺ T cells in SLE patients with renal involvement. CD4⁺CD25⁻Foxp3⁺ T cells were also detected in urine sediment samples of patients with active glomerulonephritis and correlated with the extent of proteinuria.

CD4⁺CD25⁻Foxp3⁺ T cells resemble regulatory rather than activated T cells. Comparative analysis of CD4⁺CD25⁻Foxp3⁺ T cells in SLE patients revealed a significant association of this newly described cell population with active nephritis. Therefore CD4⁺CD25⁻Foxp3⁺ T cells might serve as an important tool to recognize and monitor SLE patients with renal involvement.