The lung is affected by disorders in which natural killer (NK) cells are thought to play an important defensive role. This study, however, demonstrated that normal lung lymphocytes actually express very little NK cell activity (P < 0.001 compared with blood lymphocytes). This was true independent of the NK-sensitive target used (K562, U937, MOLT-3, or Daudi). This lack of lung lymphocyte NK activity occurred even though the proportions of lymphocytes in the normal lower respiratory tract with the morphology (large granular lymphocytes) and surface antigen markers of NK cells were similar to that of blood (P > 0.5). Although normal lung lymhocytes bound to known NK-sensitive targets, they did not lyse these cells (P < 0.001 compared with blood), which suggested that the lack of lung NK cell activity resulted from a relative inability of lung NK cells to destroy their targets. While the mechanisms of this functional impotence of lung NK cells are not clear, normal human alveolar macrophages and lower respiratory tract epithelial lining fluid exerted a profound suppressive effect on blood NK cell activity (P < 0.001 for both) by inhibiting their ability to lyse target cells after binding (P < 0.001). Though impotent initially, when incubated for 24 h in medium alone, normal lung lymphocytes demonstrated markedly enhanced NK activity (P < 0.02), which suggested that lung NK cells do have the potential to express NK activity. Interleukin-2 (IL-2) further augemented this effect (P < 0.05), but gamma interferon did not (P > 0.2). Consistent with this observation, lung lymphocytes from patients with active sarcoidosis, a disease in which lung lymphocytes are spontaneously releasing IL-2, did express NK cell activity (P < 0.01). These studies suggest that although NK cells are present in the normal lung, they are functionally inactive, due, at least in part, to local inhibitory influences. In the presence of IL-2, however, lung NK cell activity is expressed, which suggests that lung NK cell activity can be modulated.
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