Imbalance between Th17 and regulatory T-cells in systemic lupus erythematosus

Abstract

Impaired function of regulatory T-cells (Treg) leads to a failure in immune tolerance and triggers autoimmunity. We analyzed whether the deficiency in Treg in systemic lupus erythematosus (SLE) is accompanied by an increase in effector T-cell responses. We studied the frequencies of IL-17A (Th17) and IFNg (Th1) producing CD4⁺ T-cells by flow cytometric detection of intracellular cytokines in PMA/ionomycin stimulated blood lymphocytes from seven patients with active SLE, eight with SLE in remission, and 11 healthy controls. Circulating Treg were evaluated as CD4⁺CD25⁺ lymphocytes expressing FoxP3. There was no difference in the percentage of Treg cells between the groups, but their absolute counts were decreased in active SLE (5 [1&#8211;7] cells/&mu;L) compared to inactive SLE (11 [6&#8211;15]; p = 0.05) and healthy controls (16 [10&#8211;20]; p < 0.01). Both the frequency and numbers of Th1 cells were decreased in SLE compared to controls. No difference was observed in the number of Th17 cells, which resulted in a decreased Th1/Th17 ratio. In parallel, a higher Treg/Th17 ratio in healthy controls (2.2 [1.8&#8211;3.6]) compared to active SLE (1.1 [1.0&#8211;2.1]; p < 0.05) was observed. There was a correlation between the number of Treg cells and disease activity status (SLEDAI, r = &#8211;0.59). SLE patients in the active phase of the disease are characterized by a deficiency in Treg cells and decreased Treg/Th17 ratio. This suggests that the imbalance between major T-cells subsets might be responsible for an increased proinflammatory response in the exacerbation of SLE. (<i>Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 4, pp. 646&#8211;653</i>)

Keywords

• systemic lupus erythematosus
• regulatory T-cells
• Th17 cells
• Th1 cells