Human lung natural killer cells are predominantly comprised of highly differentiated hypofunctional CD69−CD56dimcells

• Published in: Journal of allergy and clinical immunology 2017-04, Vol.139 (4), p.1321
• Main Authors: Marquardt, Nicole, Kekäläinen, Eliisa, Chen, Puran, Kvedaraite, Egle, Wilson, Jennifer N, Ivarsson, Martin A, Mjösberg, Jenny, Berglin, Lena, Säfholm, Jesper, Manson, Martijn L, Adner, Mikael, Al-Ameri, Mamdoh, Bergman, Per, Orre, Ann-Charlotte, Svensson, Mattias, Dahlén, Barbro, Dahlén, Sven-Erik, Ljunggren, Hans-Gustaf, Michaëlsson, Jakob
• Format: Article
• Language: English
• Subjects: Blood circulation; Bone marrow; Cancer; Cell differentiation; Chemotherapy; Chronic obstructive pulmonary disease; Cigarette smoking; Cigarettes; Cytokines; Cytotoxicity; Defensive behavior; Drug addiction; Fetuses; Gastrointestinal tract; Genotype & phenotype; Human behavior; Hypersensitivity; Immune response; Immunological memory; Immunology; Infections; Interferon; Killer cell immunoglobulin-like receptors; Liver; Lung cancer; Lung diseases; Lymphocyte receptors; Lymphocytes; Lymphocytes B; Lymphoid tissue; Malignancy; Mice; Organs; Pathogens; Phosphates; Radiation therapy; Radiotherapy; Respiratory diseases; Respiratory tract; Rodents; Skin; Smoke; Smoking; Spleen; Stimulation; Surgery; T cell receptors; Thoracic surgery; Tumor cells; Viruses
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2016.07.043

Background In contrast to the extensive knowledge about human natural killer (NK) cells in peripheral blood, relatively little is known about NK cells in the human lung. Knowledge about the composition, differentiation, and function of human lung NK cells is critical to better understand their role in diseases affecting the lung, including asthma, chronic obstructive pulmonary disease, infections, and cancer. Objective We sought to analyze and compare the phenotypic and functional characteristics of NK cells in the human lung and peripheral blood at the single-cell level. Methods NK cells in human lung tissue and matched peripheral blood from 132 subjects were analyzed by using 16-color flow cytometry and confocal microscopy. Results CD56dimCD16+NK cells made up the vast majority of NK cells in human lungs, had a more differentiated phenotype, and more frequently expressed educating killer cell immunoglobulin-like receptors compared with NK cells in peripheral blood. Despite this, human lung NK cells were hyporesponsive toward target cell stimulation, even after priming with IFN-α. Furthermore, we detected a small subset of NK cells expressing CD69, a marker of tissue residency. These CD69+NK cells in the lung consisted predominantly of immature CD56brightCD16−NK cells and less differentiated CD56dimCD16+NK cells. Conclusion Here, we characterize the major NK cell populations in the human lung. Our data suggest a model in which the majority of NK cells in the human lung dynamically move between blood and the lung rather than residing in the lung asbona fidetissue-resident CD69+NK cells.