CD4(+)CD25(+)CD127(-) and CD4(+)CD25(+)Foxp3(+) Regulatory T Cell Subsets in Mediating Autoimmune Reactivity in Systemic Lupus Erythematosus Patients

Arch Immunol Ther Exp (Warsz). 2016 Oct;64(5):399-407. doi: 10.1007/s00005-016-0399-5. Epub 2016 May 7.

Abstract

The available clinical as well as experimental studies implicate participation of T regulatory (Treg) subsets in the pathogenesis and course of systemic lupus erythematosus (SLE). Introduction of the CD4(+)CD25(+)CD127(-) and CD4(+)CD25(+)Foxp3(+) regulatory subpopulations analysis into immunological processes assessment and disease activation prognosis in patients with lupus nephritis (LN) may improve monitoring of disease activity and enable an early, and thus more effective, therapeutic treatment. The main goal of the study was to investigate whether the quantitative changes of Treg subpopulations are related to the clinical status of patients with LN. Fifty-four adult SLE patients divided into two groups according to their SLEDAI and renal SLEDAI scores were enrolled into the study. Subpopulations of CD4(+)CD25(+)CD127(-) and CD4(+)CD25(+)Foxp3(+) phenotypes were determined by flow cytometry. The control group had higher absolute number of CD4(+)CD25(+)Foxp3(+) cells compared with the study group (p < 0.001). Also, significant inverse correlation in the absolute number of CD4(+)CD25(+)Foxp3(+) cells and SLEDAI score was observed. There were significant differences in the percentage and absolute number of CD4(+)CD25(+)Foxp3(+) lymphocytes between active and non-active LN groups. The study group had statistically lower values of CD4(+)CD25(+)CD127(-) cells, both in the percentage (p < 0.001) as well as their absolute number (p = 0.014) compared to the control group. There were also statistically significant positive correlations between the absolute number of CD4(+)CD25(+)CD127(-) and CD4(+)CD25(+)Foxp3(+) Tregs.

In conclusion: (1) reduction in the number of regulatory CD4(+)CD25(+)Foxp3(+) cells is a promising indicator of the activity of SLE, particularly of renal involvement; (2) determination of the number of regulatory cells using the CD4(+)CD25(+)CD127(-) phenotype is unreliable in patients with SLE.

Keywords: Flow cytometry; Lupus nephritis; Regulatory cells; Systemic lupus erythematosus.

MeSH terms

  • Adult
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Immune Tolerance
  • Inflammation
  • Interleukin-2 Receptor alpha Subunit / metabolism*
  • Interleukin-7 Receptor alpha Subunit / metabolism*
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism
  • Lupus Nephritis / immunology
  • Lupus Nephritis / metabolism
  • Male
  • Middle Aged
  • Phenotype
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Young Adult

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-7 Receptor alpha Subunit