Abstract

Chronic pulmonary aspergillosis (CPA) is a severe pulmonary disease caused by aspergillus fumigatus infection. However, immune responses in CPA patients remained to be elucidated. In humans, the CD4+Foxp3+regulatory T cell (Treg) population are classified into the following three subsets based on their expression of CD45RA and Foxp3: CD45RA+Foxp3lo resting Treg cells (subset I), CD45RAFoxp3high activated Treg cells (subset II), and CD45RAFoxp3locytokine-secreting non-suppressive cells (subset III). In the present study, we investigated these three CD4+Foxp3+cell subsets and their clinical implication in CPA patients.

The frequency of total CD4+Foxp3+ cells did not differ between CPA patients and healthy controls. Whereas the frequency of subset I or II also did not differ between the two groups, the frequency of subset III was significantly increased in CPA patients compared with healthy controls. Interestingly, IL-17A production was observed in the subset III CD4+Foxp3+ T cells, and the frequency of subset III significantly correlated with IL-17A production from the CD4+ T cell population. Moreover, we found that better clinical prognosis, evaluated by less hospitalization incident, was associated with higher IL-17A production from the CD4+ T cell population and higher frequency of subset III CD4+Foxp3+ cells among CPA patients.

In summary, the frequency of IL-17A-producing CD4+Foxp3+ T cells was increased and correlated with the frequency of IL-17A+ CD4+ T cells, and the higher frequency of IL-17A-producing CD4+Foxp3+ T cells was related with better clinical prognosis. We suggest that IL-17A-producing CD4+Foxp3+ T cells (subset III) may have a role in Th17 regulation and antifungal immune responses in CPA patients.

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