No abstract

SUMMARYThe age-dependent variation in the proportion and number of lymphocyte subsets was examined at various extrathymic sites, including the liver, small intestine, colon and appendix in mice. In comparison with young mice (4 weeks of age), the number of total lymphocytes yielded by all tested organs was greater in adult (9 weeks) and old (40 weeks) mice. The major lymphocyte subset that expanded with age was interleukin-2 receptor (IL-2R) b + CD3 int cells (50% of them expressed NK1.1) in the liver, whereas it was CD3 + IL-2Rb -NK1.1 -cells at all intraepithelial sites in the intestine. Although NK1.1 + CD3 + cells were present at intraepithelial sites in the intestine, the proportion of this subset was rather low. The ratio of CD4 to CD8 tended to decrease among natural killer T (NKT) cells and T cells at all intraepithelial sites in the intestine with age. A unique population of double-positive CD4 + CD8 + cells in the small intestine increased in old mice. B220 + T cells were found mainly in the appendix and colon, and the proportion of these T cells decreased in old mice. Conventional NKT cells were very few in Ja281 -/--and CD1d -/--mice in the liver, while NKT cells which existed in the appendix remained unchanged even in these mice. This was because unconventional CD8 + NKT cells were present in the intestine. The present results suggest that despite the fact that both the liver and intraepithelial sites in the intestine carry many extrathymic T cells, the distribution of lymphocyte subsets and their age-associated variation are site-specific.

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.

Background and Aim: Balloon-occluded retrograde transvenous obliteration (BRTO) has been widely adopted for the management of gastric fundal varices (GVs). There are a few reports that BRTO leads to the improvement of mid-term and long-term hepatic functional reserve (HFR). We retrospectively investigated the longterm effect on HFR and prognosis among patients who had undergone BRTO for GVs. Methods: This single-center, retrospective study included 57successful patients out of 60 patients who underwent BRTO for GVs from December 2005 to September 2018. We examined the indicators of HFR (e.g., encephalopathy and ascites statuses, serum total bilirubin and albumin levels, % prothrombin time, and Child-Pugh and albumin-bilirubin [ALBI] scores) during 3 years of follow-up after BRTO. We analyzed survival using the Kaplan-Meier method and identified the independent prognostic factors via multivariate analyses. Results: GVs disappeared in all patients who were successfully treated by BRTO. At 3 years after BRTO, serum albumin levels were significantly elevated (from 3.3 to 4.0 g/dL, P = 0.008), while Child-Pugh and ALBI scores were significantly decreased (from 7.0 to 5.7, P = 0.043, and from À1.94 to À2.60, P = 0.006, respectively). The median survival time among all patients was 2207 days; the survival rates after BRTO were 87.0% at 1 year, 81.8% at 3 years, 67.3% at 5 years, and 44.1% at 10 years. Multivariate analyses revealed that ascites, hepatic encephalopathy, and malignant neoplasms were independently associated with poor prognosis. Conclusion: BRTO for GVs has a favorable effect on long-term HFR.