Here we characterize tissue-resident NK cell subsets in human lung tissue by multicolor flow cytometry. Tissue-resident NK cells can be identified by CD69, CD103, and CD49a. Whereas on bulk level terminally differentiated NK cells are accumulated in the lung as compared to matched peripheral blood, tissue-resident lung NK cells appear immature. In 10-15% of the donors we found a clonal-like expansion of tissue-resident NK cells, and accumulation of CD69+ NK cells correlated strongly with decreased lung function. Finally, clonal-like expanded tissue-resident NK cells strongly expressed NKG2C, indicating a role for a preceding viral infection in shaping this NK cell population.
Whereas lung NK cells are normally suppressed, activated clonal-like NK cell expansions might exert bystander cytotoxicity against healthy tissue and contribute to pathological conditions. We expect that our data will help in understanding the role of NK cells in the development and progression of lung diseases and improve the diagnosis and treatment strategies.