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

Folia Histochem Cytobiol. 2011;49(4):646-53. doi: 10.5603/fhc.2011.0088.

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 [1-7] cells/μL) compared to inactive SLE (11 [6-15]; p = 0.05) and healthy controls (16 [10-20]; 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 [1.8-3.6]) compared to active SLE (1.1 [1.0-2.1]; p 〈 0.05) was observed. There was a correlation between the number of Treg cells and disease activity status (SLEDAI, r = -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.

MeSH terms

  • Flow Cytometry
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • Th17 Cells / immunology
  • Th17 Cells / metabolism*

Substances

  • Forkhead Transcription Factors