Phenotypic and functional analysis of CD4+ CD25- Foxp3+ T cells in patients with systemic lupus erythematosus.
نویسندگان
چکیده
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-gamma 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.
منابع مشابه
The Nature of Increased Circulating CD4+CD25-Foxp3+ T Cells in Patients with Systemic Lupus Erythematosus: A Novel Hypothesis
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...
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ورودعنوان ژورنال:
- Journal of immunology
دوره 182 3 شماره
صفحات -
تاریخ انتشار 2009