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Lymphocytes with cytotoxic activity have been identified in sinusoids of rat liver. We investigated the effects of aging on the cytotoxicity of liver sinusoidal lymphocytes in the rat and attempted to identify the cells responsible for cytotoxicity using a Thy1 monoclonal antibody. Natural Killer (NK) activity against YAC1 peaked at the age of 8 weeks, while cytotoxicity against NK-resistant Lymphokine Activated Killer (LAK)-sensitive P815 increased gradually with age. A cold target inhibition assay showed that lymphocytes cytotoxic for P815 and AH109 were also present in the liver sinusoids of aged rats. When these cells were fractionated by the Percoll discontinuous density gradient method, cytotoxic cells were found to comprise large granular lymphocytes (LGLs) rich in low- and middle-density fractions. Cytotoxicity against various targets increased when CD5(+) cells were removed using CD5-conjugated beads. Cytotoxicity against P815, AH109 and AH130 was decreased as compared with control lymphocytes when CD5(-) Thy1(+) lymphocytes were removed using CD5, Thy1-conjugated beads. Immunohistologic examination revealed Thy1(+) LGLs with rod-cored vesicles and electron-dense granules in the liver sinusoids. We consider that LAK-like cells with a Thy1 phenotype are present in the liver sinusoids and suggest that they have a broad range of cytotoxicity.

Thy1(+) Lymphocytes with LAK-like Activity Are Present in Rat Liver Sinusoids.