ENHANCED NATURAL BUT DIMINISHED ANTIBODY-MEDIATED CYTOTOXICITY IN THELUNGS OF MRLLPR LPR MICE/

Human systemic lupus erythematosus (SLE) patients, as well as MRLlpr/l pr mice which develop a SLE-like disease, have decreased numbers and f unctional activity of systemic natural killer (NK) cells. In contrast, it has been found that among lymphocytes recovered from the bronchoal veolar lavage fluid of SLE patients, NK cells were increased in number , correlating with the severity of the lung engagement. The present st udy was undertaken to assay the capacity for natural killing in the lu ng compartment of MRLlpr/lpr mice compared with healthy congenic MRL /+ and heterozygous MRL +/lpr mice. Cr-51-labelled YAC-1 cells were in jected intravenously to settle in the lungs where they were targeted f or lysis by NK cells. YAC-1 cell killing inversely correlated with rad ioactivity remaining in the lungs after the assay, and was inhibited b y antibody to the asialo-GM1 antigen expressed on NK cells. To analyse the capacity in the lung for cytolysis of non-NK cell-sensitive targe t cells, a similar in vivo Cr-51-release assay was set up for antibody -mediated allospecific cytotoxicity. We demonstrate that MRLlpr/lpr mi ce throughout their lifespan display significantly increased natural c ytotoxic activity in the lungs compared with MRL +/+ and MRL +/lpr mic e, as demonstrated by more efficient killing of YAC-1 cells. In contra st, antibody-mediated allospecific cytotoxicity in the lungs was signi ficantly less effective in the MRLlpr/lpr strain.