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Chronic graft‐versus‐host disease (GVHD) accompanying autoimmune disease was induced in (C57BL/6×DBA/2) F1 mice (H‐2b/d) by an injection of splenic T cells of parental DBA/2 origin (H‐2d). In parallel with the onset of proteinuria, an expansion of lymphocytes was induced in the liver and kidney, showing a peak at 2 weeks after the onset of disease. The majority of lymphocytes were of recipient origin (H‐2b/d). The main lymphocyte subset among T cells at the pre‐onset stage and after the onset of disease was CD8+ NK1.1– CD3int cells (of extrathymic, hepatic origin) in both the liver and kidney. NK1.1– CD3int cells confer primarily neither NK‐like nor NKT‐like cytotoxicity. No induction of these types of cytotoxicity was observed in these mice with the expansion of NK1.1– CD3int cells. This raised the possibility that granulocytes induced in the liver and kidney might be associated with tissue damage. The present results suggest that, similarly to the case of autoimmune‐prone mice with genetic background (e.g. MRL‐lpr/lpr mice and BXSB mice), NK1.1– CD3int cells of extrathymic, hepatic origin might be crucial lymphocytes involved in the induction of the autoimmune‐like disease in mice with chronic GVHD, in conjunction with Bcells (e.g. B‐1 cells).

The human liver contains significant numbers of innate immune cells, such as natural killer (NK) cells and natural killer T (NKT) cells, which express both T-cell receptors and NK-cell receptors simultaneously. It has been suggested that the innate immune system plays a crucial role in the liver. In this report, the distribution of NK and NKT cells in the liver and peripheral blood of two patients with drug-induced fulminant hepatic failure (FHF) who had undergone living donor liver transplantation was examined. In both the liver and peripheral blood, the proportions of NK and NKT cells markedly decreased compared with those in healthy donors. It was also revealed that, unlike murine NKT cells, human CD56(+) T cells and CD57(+) T cells did not constitutively express CD28, which is one of the important costimulatory molecules on T cells. Additionally, the residual CD56(+) T cells and CD57(+) T cells in the patients expressed more CD28 than in controls. This result suggests that NKT cells might be more activated in FHF. Although the accumulation of further cases is required, it is suggested that both NK and NKT cells might be involved in hepatic injury in FHF.

SUMMARYTAP-1 de®cient (À/À) mice cannot transport MHC class I antigens onto the cell surface, which results in failure of the generation of CD8T cells in the thymus. In a series of recent studies, it has been proposed that extrathymic T cells are generated in the liver and at other extrathymic sites (e.g. the intestine). It was therefore investigated whether CD8 extrathymic T cells require an interaction with MHC class I antigens for their differentiation in TAP-1(À/À) mice. Although CD8 thymically derived T cells were con®rmed to be absent in the spleen as well as in the thymus, CD8abT cells were abundant in the livers and intestines of TAP-1(À/À) mice. These CD8 T cells expanded in the liver as a function of age and were mainly con®ned to a NK1Á1 À CD3 int population which is known to be truly of extrathymic origin. Hepatic lymphocytes, which contained CD8 T cells and which were isolated from TAP-1(À/À) mice (H-2 b ), responded to neither mutated MHC class I antigens (bm1) nor allogeneic MHC class I antigens (H-2 d ) in in vitro mixed lymphocyte cultures. However, the results from repeated in vivo stimulations with alloantigens (H-2 d ) were interesting. Allogeneic cytotoxicity was induced in liver lymphocytes in TAP-1(À/À) mice, although the magnitude of cytotoxicity was lower than that of liver lymphocytes in immunized B6 mice. All allogeneic cytotoxicity disappeared with the elimination of CD8 cells in TAP-1(À/À) mice. These results suggest that the generation and function of CD8 extrathymic T cells are independent of the existence of the MHC class I antigens of the mouse but have a limited allorecognition ability.