Natural killer cells are present in the normal human lung but are functionally impotent

As bstract. The lung is affected by disorders in which natural killer (NK) cells are thought to play an important defensive role. This study, however, demon-strated 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 lymphocytes 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 macro-phages 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 augmented this effect (P < 0.05), but gamma interferon did not (