Different Profiles of IL-10+IFN-γ–IL-4–CD4+ T Cells in the Peripheral Blood in Atopic and Non-Atopic Asthmatics

Abstract

Background: The impaired production of interleukin (IL) 10 from regulatory T cells has been proposed as a causal mechanism of asthma. Although IL-10-producing (IL-10+) T cells are detectable in the peripheral blood, their significance in the pathophysiology of asthma remains uncertain. Objectives: This study aimed to investigate the profile of circulating IL-10+CD4+ T cells in atopic and non-atopic asthma. Methods: Atopic and non-atopic asthmatics were divided into a mild and severe group. Their peripheral blood mononuclear cells (PBMCs) were stimulated with anti-CD3 and anti-CD28 antibodies and then processed for triple cytokine flow cytometry directed to IL-10, interferon (IFN) γ and IL-4. Results: IL-10+CD4+ cells were exclusively detected in the IFN-γ–IL-4– population. In atopic asthma, the frequency of IL-10+IFN-γ–IL-4–CD4+ cells in the severe group was significantly lower than that in the mild group. The frequency of IL-10+IFN-γ–IL-4–CD4+ cells in the severe group was not significantly different from that in the mild group of those with non-atopic asthma. The frequency of IL-4+IFN-γ–IL-10–CD4+ cells (Th2) was significantly higher in the group with mild atopic asthma than in that with mild non-atopic asthma. IFN-γ+IL-4–IL-10–CD4+ cells (Th1) did not differ between groups, irrespective whether the subjects suffered from atopic or non-atopic asthma. Conclusions: IL-10+CD4+ cells in PBMCs may be distinct from Th1 or Th2 and likely have the profile of regulatory T cells. The differential association of IL-10+IFN-γ–IL-4–CD4+ cells with clinical severity between atopic and non-atopic asthma implies that its pathophysiological significance may differ among asthma phenotypes.