Increased IL-4- and IL-17-producing CD8⁺ cells are related to decreased CD39⁺CD4⁺Foxp3⁺ cells in allergic asthma

ABSTRACT

Objective: In allergic asthma, regulatory T cell (Treg) number and function are decreased. Antigen-primed CD8⁺ T cells play an indispensable role in the full development of airway inflammation and airway hyper-responsiveness (AHR) occurring in asthma. In this study, we investigated the relationship between subpopulations of CD8⁺ T cells and CD39⁺ Tregs. Methods: Female C57BL/6 mice were used to develop the model of allergic asthma. Experimental mice were immunized with ovalbumin (OVA) by intra-peritoneal (i.p) injection and then challenged with OVA by intra-tracheal administration. Control mice were immunized with vehicle by i.p injection and challenged with OVA. Airway inflammation was determined by histology and AHR was measured by an invasive method. Levels of interferon (IFN)-γ, IL-4, and IL-17 in bronchoalveolar lavage fluid (BALF) were determined by enzyme-linked immunosorbent assay. The frequencies of CD8⁺IFN-γ⁺ cells (Tc1), CD8⁺IL-4⁺ cells (Tc2), CD8⁺IL-17⁺cells (Tc17), and CD39⁺Tregs were measured by flow cytometry. The correlation between CD39⁺Tregs and Tc subsets was analyzed by Pearson’s test. Results: Experimental mice displayed phenotypes of allergic asthma, including inflammatory cell infiltration into the lungs, goblet cell hyperplasia, increased airway resistance, and increased IL-4 and IL-17 in BALF. Compared to control mice, experimental mice displayed lower CD39⁺Tregs and Tc1 but higher Tc2 and Tc17. There was a negative correlation between CD39⁺Tregs and Tc2 or Tc17. Conclusion: In allergic asthma, increased Tc2 and Tc17 are possibly related to insufficient CD39⁺Tregs.

KEYWORDS:

• Allergic asthma
• CD39⁺Tregs
• CD8⁺IFN-γ⁺cells
• CD8⁺IL-4⁺cells
• CD8⁺IL-17⁺cells

Acknowledgments

This study was supported by the National Science Foundation of China (Grant no. 81170029) and supported by the National Science Foundation of Hubei Province (Grant no. 2016CFB410). We thank the faculties at the Center for Medical Research, Hubei Key Lab of Allergy and Immune-related Disease of Wuhan University.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. This paper received no funding from outside agencies, organizations, or companies.

Funding

This study was supported by the National Science Foundation of China (Grant No. 81170029) and supported by the National Science Foundation of Hubei Province (Grant No. 2016CFB410).