Enhanced natural but diminished antibody-mediated cytotoxicity in the lungs of MRLlpr/lpr mice

Human systemic lupus erythematosus (SLE) patients, as well as MRLlpr/lpr mice which develop a SLE-like disease, have decreased numbers and functional activity of systemic natural killer (NK) cells. In contrast, it has been found that among lymphocytes recovered from the bronchoalveolar lavage fluid of SLE patients, NK cells were increased in number, correlating with the severity of the lung engagement. The present study was undertaken to assay the capacity for natural killing in the lung compartment of MRLlpr/lpr mice compared with healthy congenic MRL +/+ and heterozygous MRL +/lpr mice. 51Cr-labelled YAC-1 cells were injected intravenously to settle in the lungs where they were targeted for lysis by NK cells. YAC-1 cell killing inversely correlated with radioactivity remaining in the lungs after the assay, and was inhibited by antibody to the asialo-GM1 antigen expressed on NK cells. To analyse the capacity in the lung for cytolysis of non-NK cell-sensitive target cells, a similar in vivo 51Cr-release assay was set up for antibody-mediated allospecific cytotoxicity. We demonstrate that MRLlpr/lpr mice throughout their lifespan display significantly increased natural cytotoxic activity in the lungs compared with MRL +/+ and MRL +/lpr mice, as demonstrated by more efficient killing of YAC-1 cells. In contrast, antibody-mediated allospecific cytotoxicity in the lungs was significantly less effective in the MRLlpr/lpr strain.