Enrichment of CD4+ CD25high T cell population in patients with systemic lupus erythematosus treated with glucocorticoids

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Abstract
Objectives: To characterise and quantify the CD4+ CD25+ T cell population in patients with systemic lupus erythematosus (SLE) and to detect the possible influence of treatments and clinical manifestations. Methods: Characterisation of CD25low and CD25high CD4+ T cells from healthy controls and from patients with SLE was carried out using flow cytometry, analysing the expression of activation and differentiation markers. The percentage of both circulating cell subsets was determined in 56 controls and 110 unselected patients with SLE. Data were related to treatment during the past 3 months and to various clinical manifestations. Results: CD4+ CD25high lymphocytes from controls expressed low levels of CD69, CD154 or CD30, but also expressed glucocorticoid-induced tumour necrosis factor receptor, high levels of intracellular cytotoxin T lymphocyte-associated antigen 4, CD45RO and diminished amounts of CD4, all of which are phenotypic characteristics of natural regulatory T cells. CD4+ CD25low cells, on the other hand, expressed the highest levels of activation markers, indicating that they represent recently activated effector cells. Similarly, analysis of cells from patients with SLE showed the same two phenotypically distinguishable CD4+ CD25low and CD4+ CD25high populations, although both expressed slightly increased levels of activation markers. Quantitative analysis showed a considerably raised percentage of CD25low and, especially, CD25high cells in patients with SLE compared with controls. This increment was unrelated to clinical manifestations, but correlated with glucocorticoid treatment. Patients treated with glucocorticoids presented raised levels of CD25high cells, whereas untreated patients and those with anti-malarial or immunosuppressive drugs had levels similar to those in controls. Conclusions: The percentage of CD4+ CD25high cells was not altered in non-steroid-treated patients, whereas glucocorticoid treatment increased their frequency in patients with SLE.