Natural killer cells in mouse lung: surface phenotype, target preference, and response to local influenza virus infection

Abstract

Natural killer (NK) and natural cytotoxic (NC) cells can be recovered from the spleens of mice. NK/NC cells are thought to serve as a first line of defense (before the development of immune responses) against tumor and virus infected cells; therefore organs such as the lung that are exposed to the environment may harbor NK/NC cells. Studies reported in this manuscript characterize a population of pulmonary cells (recovered from collagenase-treated lungs) that exhibited cytotoxic activity against 51Cr-labeled tumor targets in vitro. As with the spleen cell populations, the mononuclear cells from the lung lysed the NK-sensitive target YAC-1 as well as the NC-sensitive WEHI 164.1 tumor cells in vitro. By using flow cytometry, it was observed that 15 to 20% of nylon wool-passed (NWP) lung cells and 5 to 15% of NWP spleen cells from C57BL/6 mice could bind antibody for NK cell alloantigens (NK 1.2, defined by (CE X NZB)F1 anti-CBA sera). Treatment of lung and spleen cell populations with complement and antisera to NK 1.2, asialo GM1, and Ly-5 but not Thy-1 antigens significantly decreased lung and splenic NK (YAC-1) activity. Forty-eight hours after infection of mice by intratracheal inoculation of an infectious dose of influenza virus (PR/8/34) NK activity was stimulated in the lung and not the spleen. Therefore although NK cells in the lung and spleen are similar in antigenic phenotype and target preference there appears to be a pulmonary compartment of natural resistance cells the function of which can be modulated locally. These data are consistent with the hypothesis that the lung contains a separate compartment for NK/NC cells that may participate in the defense mechanisms of the lung.