Objectives: The forkhead family transcription factor Foxp3 currently represents the most specific marker molecule for CD4+CD25+ T cells with suppressive/regulatory capacity (Treg) in the mouse. Recent studies in the human system, however, indicate that the expression of Foxp3 can be T cell activation dependent. This tempted us to evaluate the significance of Foxp3 expression under autoimmune conditions with chronic T cell activation in patients with systemic lupus erythematosus (SLE) as compared with healthy controls (HCs).
Methods: Proportions of peripheral blood CD4+Foxp3+ T cells and CD4+CD25high T cells were determined in patients with active and inactive SLE as compared with HC by flow cytometry. Comparative analysis of the percentage of CD4+Foxp3+ T cells and of percentage of CD4+CD25high T cells with clinical disease activity and T cell activation marker molecule expression were performed. Finally, the induction of Foxp3 expression was analysed upon T cell activation in vitro.
Results: Proportions of CD4+Foxp3+ T cells were significantly increased in patients with SLE as compared with HC and a significant correlation was observed between clinical disease activity and proportions of CD4+Foxp3+ T cells. On the other hand, proportions of CD4+CD25high were decreased in SLE and no correlation with a T cell activation marker expression of was observed. In addition, in vitro activation of T cells induced Foxp3 expression.
Conclusions: Our data suggest that the expression of Foxp3 on CD4+ T cells in patients with SLE, at least to some extent, reflects the activation of CD4+ T cells due to underlying disease activity and does not necessarily indicate a functional regulatory T cell capacity.
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Funding: This work was supported by grant P18374-B13 of the Austrian Science Fund (FWF).
Competing interests: None.
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