Consultant University Medicine Essen Essen, Germany
Introduction/Rationale: Cystic fibrosis (CF) is a life-limiting genetic disease associated with altered immune regulation. CFTR triple modulator therapy (elexacaftor/tezacaftor/ivacaftor, ETI) improves clinical outcomes in people with CF (pwCF) but its impact on adaptive immunity remains unclear.
Methods: We analyzed peripheral blood CD4⁺ T cells from healthy controls (n=22) and pwCF (n=21) at baseline, 3, 6, and 9 months after ETI initiation. CD4⁺ T cells were immunophenotyped by flow cytometry directly after isolation and 48 hours in vitro culture (±αCD3/CD28). Plasma cytokine levels (n=12) were quantified.
Results: At baseline, pwCF showed higher CD69⁺ and terminally differentiated effector memory (Temra) CD4⁺ T cells, along with reduced effector regulatory T cells (eTreg), suggesting chronic activation and impaired T cell regulation. ETI reduced CD69+ and Temra, while giving rise to eTregs, particularly after activation, reaching control levels. Plasma cytokines mirrored some of these changes. IL-9 and IL-10, both linked to Treg function, were lower in pwCF but increased post-ETI. Classical Th2 cytokines (IL-5, IL-13) showed similar trends, which may reflect partial recovery of Treg-associated function and Th2 response. In contrast, IL-22 remained below control levels despite ETI, suggesting epithelial barrier-associated deficits.
Conclusion: Overall, ETI not only improved clinical outcomes in pwCF but rebalanced CD4⁺ T cell subsets and cytokine profiles, suggesting improved adaptive immune function following CFTR correction.
