Clinical implications of CD4⁺ T cell subsets in adult atopic asthma patients

Background: T cells play a central role in chronic inflammation in asthma. However, the roles of individual subsets of T cells in the pathology of asthma in patients remain to be better understood. Methods: We investigated the potential signatures of T cell subset phenotypes in asthma using fresh whole blood from adult atopic asthma patients (n=43) and non-asthmatic control subjects (n=22). We further assessed their potential clinical implications by correlating asthma severity. Results: We report four major features of CD4⁺ T cells in the blood of atopic asthma patients. First, patients had a profound increase of CCR7⁺ memory CD4⁺ T cells, but not CCR7^- memory CD4⁺ T cells. Second, an increase in CCR4⁺ CD4⁺ T cells in patients was mainly attributed to the increase of CCR7⁺ memory CD4⁺ T cells. Accordingly, the frequency of CCR4⁺CCR7⁺ memory CD4⁺ T cells correlated with asthma severity. Current common asthma therapeutics (including corticosteroids) were not able to affect the frequency of CCR4⁺CCR7⁺ memory CD4⁺ T cell subsets. Third, patients had an increase of Tregs, as assessed by measuring CD25, Foxp3, IL-10 and CTLA-4 expression. However, asthma severity was inversely correlated only with the frequency of CTLA-4⁺ CD4⁺ T cells. Lastly, patients and control subjects have similar frequencies of CD4⁺ T cells that express CCR5, CCR6, CXCR3, CXCR5, CD11a, or α4 integrin. However, the frequency of α4⁺ CD4⁺ T cells in patients correlated with asthma severity. Conclusions: CCR4⁺CCR7⁺ memory, but not CCR4⁺CCR7^- memory, α4⁺, and CTLA4⁺ CD4⁺ T cells in patients show significant clinical implications in atopic asthma. Current common therapeutics cannot alter the frequency of such CD4⁺ T cell subsets in adult atopic asthma patients.