Alterations of CD4+CXCR5+Tfh cells and its transcription regulatory factors in children with asthma

Abstract:

Objective To study the alterations of follicular T helper cells (CD4⁺CXCR5⁺Tfh cells, Tfh) on circulating T lymphocytes in children with asthma, and to study the expression of transcription regulatory factors BCL-6 and BLIMP-1 mRNA. Methods Sixty-four children with asthma and 25 healthy controls were enrolled in this study. On the basis of the disease, the children with asthma were classified into acute phase group (n=36) and remission phase group (n=28). The flow cytometry was used to detect the proportion of CD4⁺CXCR5⁺Tfh cells on CD4⁺T lymphocytes. Real-time PCR was performed to detect the levels of BCL-6 mRNA and BLIMP-1 mRNA. The double-antibody Sandwich ELISA was used to detect plasma concentrations of total IgE, IL-2, IL-6 and IL-21. Results The proportion of CD4⁺CXCR5⁺Tfh cells was significantly higher in the acute group than in the control group and the remission group (P<0.05). Transcription levels of BCL-6 mRNA were significantly higher, while the inhibitory factors BLIMP-1 mRNA was significantly lower in the acute group than in the remission group and control group (P<0.05). The plasma concentration of IL-6 in the acute group increased significantly compared with the control group (P<0.05). Plasma concentrations of total IgE and IL-21 increased significantly, in contrast, plasma IL-2 concentration decreased significantly in the acute group, compared with the control group and the remission group (P<0.05). Correlation analysis showed that both IL-21 and IL-6 concentrations were positively correlated with the proportion of CD4⁺CXCR5⁺Tfh cells (r=0.76, r=0.46 respectively; P<0.05), while IL-2 level was negatively correlated with the proportion of Tfh cells (r=-0.68, P<0.05). Conclusions The abnormal proportion of CD4⁺CXCR5⁺Tfh cells might be involved in the immunological pathogenesis of acute asthma in children. The increased expression of BCL-6 mRNA and decreased expression of BLIMP-1 mRNA as well as the alterations of plasma total IgE, cytokines IL-2, IL-6 and IL-21 in microenvironment might be account for the increased proportion of CD4⁺CXCR5⁺Tfh cells in children with acute asthma.