Abundance of CD4(+) T cells and NK cells but their deficiency in anti-hepatoma cytotoxicity in the liver of LEC rats

摘要

Long-Evans Cinnamon (LEC) rats, genetically deficient in copper metabolism, develop hepatic cirrhosis (and subsequent hepatoma) with age. Immunologically, LEC rats have a maturational arrest of CD4(+) T cells from double-positive CD4(+)8(+) cells in the thymus. Despite this fact, some CD4(+) T cells are always present in peripheral immune organs of LEC rats, suggesting that CD4(+) T cells are generated extrathymically. Data on levels of CD4(+) T cells in the liver, thymus and other organs of LEC rats indicated that extrathymic CD4(+) T cells may be usually intensively generated in the liver. However, liver MNC (comprised of T cells and NK cells) completely lacked cytotoxicity against syngeneic hepatoma cells. The major effector cells against such hepatoma cells are CD3(-) CD8(+) NK cells in control rats. No difference between control rats and LEC rats was observed in the morphology and proliferative response of liver MNC. These results suggest that a number of extrathymic T cells and NK cells are normally generated but are functionally defective and, therefore, permit the spontaneous onset of hepatoma. This functional defect of liver MNC may be due to an abnormal microenvironment in the liver of LEC rats.