Phenotypic characterization of ex vivo CD4+CD25highCD127low immune regulatory T cells in allergic asthma: pathogenesis relevance of their FoxP3, GITR, CTLA-4 and FAS expressions

J Biol Regul Homeost Agents. 2012 Oct-Dec;26(4):627-39.

Abstract

Background: CD4+CD25high regulatory T (Treg) cells are crucial for immune homeostasis and peripheral tolerance, but their relevance to allergic asthma has not been fully elucidated.

Objective: To assess peripheral blood CD4+ T cells, and CD4+CD25highCD127low Treg cells expressing phenotypic markers (FoxP3, GITR, CTLA-4, and FAS) in allergic asthma subjects.

Materials and methods: Peripheral blood mononuclear cells were isolated from 60 allergic asthma (AA) subjects and 30 healthy controls (HC). We examined by flow cytometry, the proportion of CD4+ T cells and CD4+CD25highCD127low Treg cells as well as the expression of FoxP3, GITR, CTLA-4, and FAS by CD4+CD25highCD127low Treg cells. Moreover, FOXP3 mRNA expression was measured by quantitative real time polymerase chain reaction (real-time RT-PCR).

Results: The absolute number of CD4+CD25highCD127low Treg cells and the percentages of CD4+CD25highCD127low Treg cells expressing one of the four selected markers were significantly lower in allergic asthma subjects compared with controls. We observed no significant decreased absolute CD4+ T cell count in the examined groups compared to the control group. Except for GITR, circulatory CD4+CD25highCD127low Treg cells of severe allergic asthma (SA) subjects showed significantly lower expressions of FoxP3, CTLA-4, and CD95 than did those isolated from mild to moderate asthma (MA) patients. There was no statistically significant difference in the level of mRNA FoxP3 expression in CD4+CD25+ Treg cells between allergic asthma subjects and healthy controls groups, and within the examined groups (p>0.05).

Conclusions: These findings suggest that allergic asthma and the use of glucocorticosteroids are associated with decreased absolute number of circulatory CD4+CD25highCD127low Treg cells and the decreased frequencies of CD4+CD25highCD127low Treg cells expressing one of the four selected markers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asthma / drug therapy
  • Asthma / immunology*
  • CD4 Lymphocyte Count
  • CTLA-4 Antigen / blood*
  • Female
  • Forkhead Transcription Factors / blood*
  • Forkhead Transcription Factors / genetics
  • Glucocorticoid-Induced TNFR-Related Protein / blood*
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunophenotyping
  • Interleukin-7 Receptor alpha Subunit / blood*
  • Male
  • Middle Aged
  • RNA, Messenger / analysis
  • T-Lymphocytes, Regulatory / immunology*
  • fas Receptor / blood*

Substances

  • CTLA-4 Antigen
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Glucocorticoid-Induced TNFR-Related Protein
  • Glucocorticoids
  • Interleukin-7 Receptor alpha Subunit
  • RNA, Messenger
  • TNFRSF18 protein, human
  • fas Receptor