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 CR7(-) 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 alpha 4 integrin. However, the frequency of alpha 4(+) CD4(+) T cells in patients correlated with asthma severity. Conclusions: CCR4(+) CCR7(+) memory, but not CCR4(+) CCR7(-) memory, alpha 4(+), 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.