A major site of extrathymic T cell differentiation exists in the liver. We investigated herein the responses of such extrathymic T cells in mice bearing syngeneic tumor cells. To identify extrathymic T cells (i.e., intermediate TCR cells), several new methods were introduced. When C57BL/6 mice were subcutaneously injected with 1 x 10(6) MCA105 tumor cells of syngeneic origin, a prominent increase in the number of hepatic MNC was induced at the initial period, i.e., until 2 weeks after tumor inoculation. The number of hepatic MNC then decreased gradually. On the other hand, the number of thymocytes began to decrease 20 days after the injection, whereas the number of splenic lymphocytes increased due to the occupation of macrophages. Analysis of the surface phenotypes revealed that the increase in the number of hepatic MNC was accompanied by an increase in the proportion of intermediate TCR cells and an induction of tumor-specific cytotoxicity in the liver. Intermediate TCR cells consisted of double-negative CD4-8- cells and single-positive CD4+ or CD8+ cells, and highly expressed IL-2 receptor beta chains and LFA-1 antigens. Interestingly, the extrathymic T cell activation in the liver and profound thymic atrophy were not induced by the injection of allogeneic tumor cells or virally transformed syngeneic tumor cells. These results suggest that extrathymic T cells, rather than CTL of thymic origin, may play important roles in host immune responses against regular syngeneic tumors.
