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Phenotypic and Functional Analysis of CD4⁺CD25^–Foxp3⁺ T Cells in Patients with Systemic Lupus Erythematosus¹

Division of Rheumatology, Internal Medicine III, General Hospital of Vienna, Medical University of Vienna, Vienna, Austria

CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Treg) that specialize in the suppression of immune responses might be critically involved in the pathogenesis of autoimmune diseases. Recent studies have described increased proportions of CD4⁺Foxp3⁺ T cells that lacked expression of CD25 in systemic lupus erythematosus (SLE) patients but the suppressive capacity of these cells has not been analyzed so far. We therefore performed combined phenotypic and functional analyses of CD4⁺CD25^–Foxp3⁺ T cells in patients with autoimmune diseases and healthy controls (HC). Phenotypic analysis revealed increased proportions of CD4⁺CD25^–Foxp3⁺ T cells in SLE patients as compared with patients with systemic sclerosis, rheumatoid arthritis, (RA), or HC. In addition, increased proportions of CD4⁺CD25^–Foxp3⁺ T cells correlated with the clinical disease activity and the daily cortisone dose. According to phenotypic analysis, CD4⁺CD25^–Foxp3⁺ T cells resembled regulatory T cells rather than activated T cells. For functional analysis, a surrogate surface marker combination to substitute for intracellular Foxp3 was defined: CD4⁺CD25^–CD127^– T cells from SLE patients were isolated by FACS sorting and analyzed for their suppressive capacity in vitro. CD4⁺CD25^–CD127^– T cells, that contained up to 53% Foxp3⁺ T cells, were found to suppress T cell proliferation but not IFN- production in vitro. In summary, CD4⁺CD25^–Foxp3⁺ T cells phenotypically and to a certain extent also functionally resemble conventional Treg. Despite increased proportions, however, their selective functional defects might contribute to the failure of Treg to control autoimmune dysregulation in SLE patients.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grant P18374-B13 of the Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung).

² Address correspondence and reprint requests to Dr. Clemens Scheinecker, Division of Rheumatology, Internal Medicine III, General Hospital of Vienna, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Wien, Austria. E-mail address: clemens.scheinecker{at}meduniwien.ac.at

³ Abbreviations used in this paper: Treg, regulatory T cell; SLE, systemic lupus erythematosus; RA, rheumatoid arthritis; SSc, systemic sclerosis; HC, healthy control; SLEDAI, SLE disease activity index; Cy, cyanin; GITR, glucocorticoid-induced TNFR.

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