Biomedical subjects

Toru Abo

Publications and source records attributed to Toru Abo.

42 records · Page 3Linked to original sources

PubMed2002

Leukocyte accumulation and changes in extra-renal organs during renal ischemia reperfusion in mice.

Multiorgan failure is a life threatening complication in patients with ischemic acute renal failure (ARF). However, little is known about the underlying multiorgan system cellular immunity in ischemic ARF. We therefore studied the dynamics of cells accumulating in the kidneys and other organs in mice and analyzed the characteristics of the accumulated cells. We prepared a unilateral renal ischemia/reperfusion injury (IRI) model in C57BL/6 or C3H/He mice. At 1 to 3 hours after renal ischemia, increased accumulations of neutrophils and intermediate T cells were observed in the clamped kidney, but the same phenomena were also observed in the nonclamped kidney, liver, and spleen. After 24 hours, these cell numbers had returned to preischemic levels, but remained elevated for a longer period in the clamped kidney. The intermediate T cells that accumulated in the kidney and liver in the IRI mice expressed higher Vbeta chains specific to forbidden clones than in the control mice. Moreover, the accumulated intermediate T cells in the IRI liver had cytotoxic activity against both tumor cells and syngeneic thymocytes. In the clamped kidney, the accumulated intermediate T cells had less cytotoxic activity against tumor cells; however, the expression of the Fas ligand (FasL) increased, indicating a cell-mediated tissue injury via the Fas/FasL system. Histopathologically, an influx of neutrophils and lymphocytes was observed not only in the clamped kidney but also in the hepatic sinusoids concomitantly with liver dysfunction. These findings indicate that a systemic cellular immune response, including intermediate T cells, affects multiple organs during ischemic ARF, which may play an important role in the development of multiorgan failure.

Alanine Transaminase↗

PubMed2002

Extrathymic T cells in malaria protection, including evidence for the onset of erythropoiesis in the liver during infection.

This review proposes the possibility that malarial protection might not be achieved through the process of acquired immunity in which the constituents are conventional T and B (B-2) cells. On the other hand, malarial protection might be achieved by the process of innate immunity in which the constituents are extrathymic T cells and autoantibody-producing B-1 cells. Accordingly, mice infected with malaria exhibited severe thymic atrophy, and the expansion of IL-2Rbeta+ CD3int cells and its subset of NK1.1-CD3int cells were simultaneously induced. In parallel with the expansion of extrathymic T cells in the liver, extramedullary erythropoiesis was found to begin in the liver of these mice. Interestingly, malarial protozoa were primarily seen in only these nucleated erythrocytes in the liver at the early stage of infection. These results suggest that malaria immunology falls into a new field of immunology, namely, innate immunity. The similarity of the immune states among malaria, aging, and autoimmune diseases also suggest that the immunosuppression of a conventional, acquired immune system is more likely the common mechanism underlying these diseases or physiological responses.

Animals↗

PubMedDate not supplied

Identification of effector cells for TNFalpha-mediated cytotoxicity against WEHI164S cells.

WEHI164S cells were found to be very sensitive targets for in vitro killing in a 6-h culture when liver or splenic lymphocytes were used as effector cells in mice. Of particular interest, a limiting cell-dilution analysis showed that effector cells were present in the liver with a high frequency (1/4,300). In contrast to YAC-1 cells as NK targets, perforin-based cytotoxicity was not highly associated with WEHI164S killing. The major killer mechanism for WEHI164S targets was TNFalpha-mediated cytotoxicity. By cell sorting experiments, both NK cells and intermediate T cells (i.e., TCR(int) cells) were found to contain effector cells against WEHI164S cells. However, the killer mechanisms underlying these effector cells were different. Namely, NK cells killed WEHI164S cells by perforin-based cytotoxicity, TNFalpha-mediated cytotoxicity, Fas ligand cytotoxicity, and other mechanisms, whereas intermediate T cells did so mainly by TNFalpha-mediated cytotoxicity. These results suggest that TNFalpha-mediated cytotoxicity mediated by so-called natural cytotoxic (NC) cells comprised events which were performed by both NK and intermediate T cells using somewhat different killer mechanisms. Intermediate T cells which were present in the liver were able to produce TNFalpha if there was appropriate stimulation.

Animals↗

PubMedDate not supplied

Morphologic examination of CD3-CD4(bright) cells in rat liver.

Recently, we found CD3-CD4(bright) cells with comparative specificity for normal rat liver. In the current study, we investigated the type and form of both CD3-CD4(bright) cells and CD3-CD4(dull) cells in the rat liver. The surface phenotype of hepatic mononuclear cells in Lewis rats was identified by using monoclonal antibodies including anti-CD4, anti-CD3, and antimacrophage in conjunction with two- or three-color immunofluorescence analysis. CD3-CD4(bright) cells and CD3-CD4(dull) cells were examined morphologically using May-Giemsa staining and scanning electron microscopy. The distribution of CD3-CD4(bright) cells and CD3-CD4(dull) cells 48 hours after intravenous administration of liposome-encapsulated dichloromethylene diphosphate was also investigated. In comparison to CD3-CD4(dull) cells, CD3-CD4(bright) cells were slightly larger macrophages with abundant cytoplasmic granules, being present with comparative specificity for normal rat liver and showing negligible effects by intravenous liposome-encapsulated dichloromethylene diphosphate administration. These data suggest that in normal young rat liver these CD3-CD4(dull) and CD3-CD4(bright) cells may be dendritic cells and Kupffer cells that shift from the liver to the spleen or vice versa. These cells may also be able to locally proliferate in liver or spleen due to changes in the developing liver.

Animals↗

PubMedDate not supplied

Macrochimerism of donor type CD56+ CD3+ T cells in donor specific transfusion via portal vein following living related donor liver transplantation.

Antigens given orally or through the portal vein are known to be less immunogenic and to induce immunologic unresponsiveness. The mechanisms responsible for graft enhancement are still unclear. Moreover, in actuality, it is difficult to perform transfer of donor antigens via the portal vein in clinical transplantation. We investigated the effect of transfer of donor blood via the portal vein intra- and post-operatively in living related donor liver transplantation for recurrent multiple hepatocellular carcinoma. A 62-year-old female, who suffered from recurrent multiple hepatocellular carcinoma with hepatitis C virus, underwent living related donor liver transplantation with the right lobe of her daughter. Eleven hepatocellular carcinomas were recognized in the resected specimen. Donor blood was administered via the portal vein using a catheter inserted in the middle colic vein intra- and postoperatively. Mononuclear cells were obtained by operative liver biopsy or postoperative biopsy using fine needle aspiration biopsy, and from peripheral blood. They were analyzed by two or three color-flow cytometry using several antibodies. The differentiation between donor and recipient was estimated by means of anti-HLA antibodies of donor and recipient. The postoperative course was uneventful. She did not suffer from acute cellular rejection and was discharged on day 30 the after operation. CD56+ CD3+ T cells in the liver increased notably from 20% to 50% after transplantation. One half of the CD56+ CD3+ T cells in the liver graft were of the donor type (donor anti-HLA A2 antibody) on day 8 after surgery. Donor type CD56+ CD3+ T cells occupied 17.4% of the total CD56+ CD3+ T cells even on day 42 after the operation. Stimulation index by mixed lymphocyte reaction continued at a low level (< 2) from day 1 after the operation. Steroids were discontinued after 40 postoperative days. FK506 was also reduced to 0.5 mg/day 4 months after the operation. There was no recurrence of hepatocellular carcinoma and hepatitis C virus for two years after the operation. Macrochimerism of donor type CD56+ CD3+ T cells in a graft might be induced by the transfer of donor blood via the portal vein and may play an important role in transplantation tolerance. Inoculation of donor blood via the portal vein may also be very useful for rapid reduction of immunosuppression.

Blood Transfusion↗

PubMedDate not supplied

Wall shear stress and intrahepatic leukocytes of graft in living related donor liver transplantation.

BACKGROUND/AIMS: We investigated the influence of HTK solution against natural killer T cells and thymic T cells in liver graft before and after perfusion in adult living related donor liver transplantation. METHODOLOGY: Graft samples were obtained before liver resection, after perfusion, and one hour after liver transplantation. Flowcytometry analysis was conducted using several human natural killer markers; CD16, CD56, CD57, and CD161. RESULTS: Natural killer T cells existed prominently in the liver leukocytes compared with their presence in peripheral blood lymphocytes, and the difference was significant. CD56+ T and CD161+ T cells, in comparison with CD16+ T cells and CD57+ T cells, were especially numerous in the liver. The proportion of CD56+ T and CD161+ T cells increased in the graft immediately after perfusion with HTK solution. However, CD16+ T cells and CD57+ T cells decreased in the graft immediately after perfusion and reperfusion of portal blood flow. Thymus-derived cells also decreased significantly after perfusion. The proportion of CD56+ T cells among CD3+ cells showed a significant increase immediately after perfusion. All types of natural killer cells in the graft immediately increased after perfusion by HTK solution and reperfusion of portal blood flow. Compared with CD57+ NKT cells, CD56+ NKT cells showed a significant tendency to stay in the liver graft against the perfusion. CD57+ NKT cells tended to wash out from the liver into the systemic circulation. Moreover, thymus-derived T cells showed the strongest tendency to wash out from the liver graft. CONCLUSIONS: CD56+ NKT cells and natural killer cells are more involved in local immunity, whereas thymus-derived cells and CD57+ NKT cells are involved in regulation of systemic immunity. Alloimmunity between local and systemic systems may be affected by the dynamic changes in hepatic circulation associated with living related donor liver transplantation.

Adolescent↗