T Cell Senescence: A Possible New Phenotype in Patients with Asthma

<bold>Background:</bold> Adaptive immune cells, especially T cells, play an important role in the pathogenesis of asthma. Cellular senescence may also play a key role in asthma; however, the relationship between T cell senescence and asthma is unclear. <bold>Objective:</bold> This study aimed to investigate whether there are different degrees of T cell senescence in patients with different asthma subtypes and healthy controls to explore the clinical correlation between T cell senescence and asthma. <bold>Methods:</bold> Using flow cytometry, we analyzed the proportions of senescent T cells (Tsens) and different subsets of helper T cells and Treg in the peripheral blood of 50 patients with asthma and 14 healthy controls and compared the proportions of Tsens among patients with asthma of different age, sex, BMI, and asthma types (such as eosinophilic and neutrophilic). In addition, we also constructed a House dust mite-induced asthma mouse model and detected the proportion of Tsens in the lung and spleen tissues of mice via flow cytometry. <bold>Results:</bold> We found that CD4⁺ Tsens levels were significantly higher in patients with asthma than in healthy controls, whereas CD8⁺ Tsens levels were not significantly different. In addition, among all patients with asthma, CD4⁺ Tsens levels were significantly higher in patients with FeNO > 25 ppb than in patients with FeNO < 25 ppb. The percentage of CD4⁺ Tsens was positively correlated with Th2 cells and FeNO. Finally, we observed significantly increased levels of CD4⁺ Tsens in the lung of asthmatic mice. <bold>Conclusions:</bold> We showed that CD4⁺ T cell senescence may be a new phenotype in patients with asthma. Type 2 inflammation in asthma may be the driver of accelerated T cell senescence.