Regulatory T-cell and T-helper 17 balance in chronic lymphocytic leukemia progression and autoimmune cytopenias

Leuk Lymphoma. 2015;56(8):2424-8. doi: 10.3109/10428194.2014.986479. Epub 2015 Jan 21.

Abstract

The reasons for progression and autoimmune cytopenias (AIC) in chronic lymphocytic leukemia (CLL) are not entirely clear, with previous studies suggesting a role for regulatory T-cells (Treg). In this study we prospectively studied Treg (CD3+CD4+CD25highCD127low), interleukin-10 (IL-10) producing Treg and T-helper 17 (Th17) (CD3+CD4+IL-17+) cells in 40 treatment-naive patients with CLL. The percentage of Th17 and not Treg cells was significantly higher in the AIC cohort than in those without AIC (p<0.0001). The Treg:Th17 ratio was skewed in favor of Th17 in the AIC cohort (p=0.02). Th17 cells are responsible for AIC of CLL. Analysis of lymph-node aspirates showed that the percentage of Treg and IL-10 expression in Treg and not Th17 was significantly higher than in peripheral blood (p<0.01). Treg cells play a major role in the microenvironment where disease progression occurs. This shows the importance of maintaining the Treg:Th17 equilibrium, for imbalance leads to CLL progression or AIC.

Keywords: Autoimmune cytopenia; T-helper 17; chronic lymphocytic leukemia; regulatory T-cells.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Surface / metabolism
  • Autoimmunity*
  • Biomarkers
  • Case-Control Studies
  • Cellular Microenvironment / immunology
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Gene Expression
  • Humans
  • Immunophenotyping
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Leukemia, Lymphocytic, Chronic, B-Cell / blood
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / mortality
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology*
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Pancytopenia / blood
  • Pancytopenia / immunology*
  • Prognosis
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism

Substances

  • Antigens, Surface
  • Biomarkers
  • Interleukin-10