@article{oai:niigata-u.repo.nii.ac.jp:00006425, author = {Seki, Shuhji and Takeda, Kazuyoshi}, issue = {3}, journal = {Acta medica et biologica, Acta medica et biologica}, month = {Sep}, note = {Few T cells with NK cell markers are present in the periphery (including the peripheral blood), but mouse livers contain a remarkably high proportion of αβ T cells with an NK cell marker, NK1.1 Ag (NK1). Interleukin 12 (IL-12), when administered into both euthymic and athymic B6 mice, endows a potent cytotoxicity to liver mononuclear cells (MNC) and inhibits liver metastases of i. v. injected liver metastatic tumors. NK1^+ αβ T cells are the main antitumor cytotoxic effectors induced by IL-12 in the liver. Interestingly, although the hepatic vein blood and lung usually do not contain NK1^+ αβ T cells, IL-12 administration induces these cells in both sites. The cells induced by IL-12 in the lung also show strong antitumor cytotoxicity and are antimetastatic effectors against i. v. injected lung metastatic tumors. In vivo IL-12 activated liver MNC (but not splenocytes), when adoptively transferred into other tumor preinjected mice, inhibited metastases in the lungs and liver. This antimetastatic effect was inhibited by the depletion of either NK1^+ cells or CD3^+ cells from IL-12 activated hepatic MNC before transfer. Depletion of NK cells in vivo by anti-asialo GM1 Ab did not reduce IL-12 induced cytotoxicity of the liver or lung MNC or antimetastasis in either organ. Depletion of both NK cells and NK1^+ αβ T cells by anti-NK1 Ab greatly inhibited the augmentation of the cytotoxicity of liver and lung MNC induced by IL-12 as well as antimetastasis in either organ. These findings show that NK1^+ αβ T cells in the mouse liver are antitumor and antimetastatic effectors which move to other organs to inhibit tumor metastases. Human livers also contain high proportions of T cells with an NK cell marker, CD56. Although human peripheral blood lymphocytes (PBL) contain a small percentage of CD56^+ αβ T cells, when monocyte depleted PBL were cultured with a combination of IL-12 and IL-2, populations of either CD56^+ αβ T cells or CD56^+ γδ T cells with potent antitumor cytotoxicity were selectively expanded. These cells had a much stronger cytotoxicity than CD56^- T cells activated IL-2 alone. Taken together, our findings demonstrate that T cells with NK cell markers likely represent a more potent antitumor and antimetastatic effector population than NK cells or conventional T cells in mice as well as in humans.}, pages = {117--133}, title = {The Antitumor Function of Extrathymic T Cells with an NK Cell Marker in the Mouse Liver and their Putative Counterpart in Humans}, volume = {44}, year = {1996} }