ITHASBEEN well established that the spleen is an important immune organ, serving as a large phagocytic filter and a major site of antibody production. The IgM-specific antibody, generated primarily in the spleen, 1 promotes opsonized phagocytosis by activating various complement fragments, and thus contributes to the early immune response to pathogens. In addition, the spleen produces tuftsin, which is a tetrapeptide regulating the activity and migration responses of phagocytic cells. 2 Splenectomy impairs normal immune function by reducing phagocytic activity, lowering serum IgM and tuftsin levels, and diminishing suppressor T-cell numbers. 3 Hence, patients with splenectomy have been shown to bear a higher risk of overwhelming postsplenectomy infection. 4,5 This provokes interest in developing alternative operative methods for splenic preservation. Autotransplantation of splenic fragments after splenectomy has been advocated as a method of retaining normal splenic immune function in the treatment of massive splenic trauma or splenomegaly caused by hematologic disorders.6-9 However, it remains equivocal whether splenic autotransplantation may help maintain splenic immune function in patients with portal hypertension and cirrhosis. Therefore, we conducted a prospective randomized study to evaluate the influence of autologous splenic transplantation in patients with portal hypertension and cirrhosis on splenic immune function, as assessed by levels of serum IgM and tuftsin.

HEPATOCYTE transplantation (HTx) has been proposed as a potential therapeutic modality for various liver disorders by providing metabolic support during acute and chronic liver failure and replacing specific liver functions in inherited metabolic liver diseases. However, after allogenic HTx into the spleens, the transplanted cells are rejected within a few days without immunosuppression.1 It has been documented that activation of cytotoxic T lymphocytes (CTL), engaging the Fas-mediated or perforin/granzyme cytolytic pathway, are responsible for the apoptosis of transplanted hepatocytes.2 On activation, CTL release perforin and granzyme B by exocytosis, and perforin facilitates the entry of granzyme B that induce apoptosis in target cells.3 Granzyme B inhibitor I antagonizes the activity of granzyme B, and may inhibit apoptotic cell death mediated by this pathway.4 Upregulation of granzyme B has been associated with the development of acute rejection in liver transplantation. The present study was designed to investigate the protective effects of granzyme B inhibitor I on allogeneic hepatocytes transplanted into rat spleens or cocultured with CTL.

Summary Expression of membrane-bound Fas ligand (mFasL) on colon cancer cells serves as a potential mechanism to inhibit host immune function by inducing apoptosis of host lymphocytes. Membrane-bound FasL can be cleaved and released as a soluble mediator (sFasL), which may spread the apoptosis induction effect. Our study examined whether colon adenocarcinoma cells release sFasL, and induce apoptosis of host lymphocytes without direct cell–cell contact. In 12 consecutive patients with colon adenocarcinoma mFasL was identified in the tumours, sFasL was measured in the sera and apoptosis identified in tumour-infiltrating and peripheral blood lymphocytes. To analyse the function of sFasL, colon cancer cells were primarily cultured; sFasL was isolated from supernatants, measured, incubated with Fas-bearing Jurkat cells, and the resulting apoptosis was analysed. Serum levels of sFasL were significantly elevated in all colon cancer patients with mFasL expression in tumour tissues (n=8). In these patients, the number of apoptotic lymphocytes was significantly increased within tumour and peripheral blood. Furthermore, sFasL was present in the corresponding supernatants and induced apoptosis of Jurkat cells in a dosedependent manner. These findings suggest that mFasL-positive colon cancer cells release sFasL, and thus may induce apoptosis of host lymphocytes as a potential mechanism for immune evasion.

Background. Donor hepatocyte apoptosis that is induced by host cytotoxic T lymphocytes (CTLs) limits the application of hepatocyte transplantation. Hepatocytes from Bcl-2 transgenic mice can resist the lethal effect of anti-Fas antibody. However, the anti-apoptotic effect of Bcl-2 expression on allogeneic transplanted hepatocytes remains illusive. This study tested the feasibility of Bcl-2 gene transfer as an approach to inhibit CTL-mediated apoptosis in allogeneic transplanted hepatocytes. Methods. An adenovirus vector that encoded human Bcl-2 gene (AdCMVhBcl-2) was used to transfect cultured rat hepatocytes, which were then transplanted into allogeneic spleens. DNA fragmentation and caspase-3 activation were examined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay and immunohistochemistry for active caspase-3, respectively. Cocultivation of hepatocytes and allogeneic CD8+ T lymphocytes was performed, and cytotoxicity on hepatocytes was examined by alanine transaminase release. Results. Bcl-2 gene transfer inhibited apoptosis and increased liver-associated enzyme activities in allogeneic transplanted hepatocytes, which were associated with inhibition of caspase-3 activation. Alanine transaminase release in hBcl-2 modified hepatocytes was lower compared with controls, which could not be further decreased by inhibition of Fas ligand and granzyme B. Conclusions. Adenovirus-mediated Bcl-2 gene transfer blocks CTL-mediated apoptosis in allogeneic hepatocytes by inhibition of caspase-3 activation. Bcl-2 gene transfer could be used to promote survival of transplanted hepatocytes.

Background: It has been demonstrated that colorectal carcinomas rarely metastasize to diseased livers. However, this phenomenon has not been thoroughly evaluated in patients with various forms of chronic hepatitis B virus (HBV) infection. Therefore, the present study examined the relationship between the incidence of hepatic metastasis of colorectal carcinomas and chronic HBV infection, with emphasis on the influence of HBV viral replication and chronic liver damage. Methods: We analyzed the clinicopathological data of 512 patients undergoing surgical treatment of colorectal carcinomas at our department from 1992 to 1998. Among these cases, 74 had chronic HBV infection, including 28 cases with HBV replication and 21 with chronic liver damage. Results: The incidence of liver metastasis in the HBV infection group (13.5%) was significantly lower than that of the noninfection group (27.1%, P, 0.05). In addition, patients with HBV infection survived longer than those without infection (P 5 0.018). Furthermore, liver metastatic rate in patients with HBV replication (3.6%) was lower than those without virus replication (19.6%, P, 0.05). In contrast, there was no significant difference in liver metastasis between HBV infected patients with or without chronic liver damage (P .0.05). Conclusions: Chronic HBV infection with viral replication reduces hepatic metastasis of colorectal cancer, and thus prolongs the survival of patients.