Adaptive immunity impairment in bronchiectasis: crosstalk of immunomodulatory cells and lymphocytes

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Background: In the context of immune dysregulation accompanying bronchiectasis, myeloid-derived suppressor cells (MDSCs) are increased and correlated with neutrophilic inflammation and disease severity, while regulatory T cells (Tregs) are exhausted, probably predisposing to exacerbations. However, adaptive immunity in bronchiectasis, especially in relation to immunomodulatory cells, has not been investigated yet. Methods: Circulating populations of helper and cytotoxic T, B, and NK cells were quantified with flow cytometry in 9 stable bronchiectasis patients and 10 healthy controls. The crosstalk of lymphocytes with immunomodulatory cells was investigated by conducting 72-hour cultures of CFSE-stained PBMCs, with/out MDSC enrichment. T cell proliferation was quantified via CFSE signal and Tregs induction was measured via flow cytometry. Results: Interestingly, B cells were significantly decreased in patients (mean±SD: 1.9%±1.4) compared to controls (2.92%±1.15, p=0.0279), while no statistically significant differences were detected in other lymphocytic populations. Proliferation of T cells was shown to be suppressed by MDSCs in a similar manner to controls (mean suppression 27% in patients vs 31.5% in controls). However, the induction of Tregs in bronchiectasis was impaired (FoxP3+ cells in CD4+CD25+ cells increased by 0.08% in patients vs 24.86% in controls), further indicating Tregs exhaustion. Conclusions: Our preliminary data suggest that, besides innate, adaptive immunity is impaired in bronchiectasis, including altered quantitative and qualitative characteristics, also attributed to interactions of these cells with defective immunomodulatory cells. *NB & AMM contributed equally

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