Circulating CXCR5+CD4+ T cells participate in the IgE accumulation in allergic asthma

Abstract

The pathogenesis of allergic asthma is primarily characterized by abnormality in immunoglobin(Ig)E pathway, suggesting a possible role for follicular helper T cells (Tfh) in the genesis of excessive IgE accumulation. The blood chemokine (C-X-C motif) receptor 5 (CXCR)5⁺CD4⁺ T cells, known as "circulating" Tfh, share common functional characteristics with Tfh cells from germinal centers. The aim of this study was to determine the phenotypes and functions of circulating CXCR5⁺CD4⁺ T cells in allergic asthmatics. Here we found the frequency of the circulating CXCR5⁺CD4⁺ T cells was raised in allergic asthma compared with healthy control (HC). Phenotypic assays showed that activated circulating CXCR5⁺CD4⁺ T cells display the key features of Tfh cells, including invariably coexpressed programmed cell death (PD)-1 and inducible costimulator (ICOS). The frequency of interleukin IL-4⁺-, IL-21⁺-producing CXCR5⁺CD4⁺ T cells was increased in allergic asthma patients compared with HC. Furthermore, sorted circulating CXCR5⁺CD4⁺ T cells from allergic asthma patients boosted IgE production in coculture assay which could be inhibited by IL-4 or IL-21 blockage. Interestingly, IL-4⁺-, IL-21⁺-CXCR5⁺CD4⁺ T cells positively correlated with total IgE in the blood. Our data indicated that circulating CXCR5⁺CD4⁺ T cells may have a significant role in facilitating IgE production in allergic asthma patients.

Keywords: Allergic asthma; CXCR5; Follicular helper T; IL-21; IL-4.