Importance of hepatic lymphocytes on innate immunity

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Malarial parasites are intracellular pathogens and therefore invade erythrocytes and hepatocytes. In this respect, conventional T and B cells could not function against the parasites. Inversely, extrathymic T cells and B-1 cells attack such parasites by their autoreactivity and autoantibodies. These evidences were produced in both murine and human studies. We also found that erythropoiesis was induced in the liver of mice after malarial infection. It is speculated that fresh erythrocytes produced in the liver might be an important target for the parasites. TAP-1(-/-) mice with missing self were also used in this study and extrathymic T cells were abundant in these mice. Innate immunity mediated by extrathymic T cells is found to be importance to eliminate missing self. A similar phenomenon was also seen in mice with stress and in mice with amyloidosis. Granulocytes are also important in parallel with extrathymic T cells and B-1 cells. In 2004, anti-erythropoietin antibody was found to cure malaria when injected into mice with malaria. In 2005 final year, the activation of NKT cells by α-GalCer induced hepatic failure. This result indicated that overactivation of NKT cells is able to induce tissue damage. NK1.1-TCR^<int> cells are also found to be a major lymphocyte subset in malarial infection.