The immunoregulatory roles of natural killer T cells in cyclophosphamide-induced tolerance.

Background: Recent studies have indicated that natural killer T (NKT) cells are essential for the establishment of transplantation tolerance. In the present study, we have elucidated the role of recipient and donor NKT cells in cyclophosphamide (CP)-induced tolerance.

Method: DBA/2 (DBA; H-2) mice were used as donors and BALB/c (BALB; H-2) wild-type (WT) or Valpha14 NKT-knockout (KO, BALB/c background) mice were used as recipients.

Effects of cyclosporin A on the activation of natural killer T cells induced by alpha-galactosylceramide.

Background: Natural killer T (NKT) cells play crucial roles in preventing autoimmune diseases and inducing transplantation tolerance. We investigated whether cyclosporin A (CsA), which is generally used in clinical transplantation and autoimmune disease therapy, could modulate the NKT cell activation induced by alpha-galactosylceramide (alpha-GalCer) treatment.

Methods: C57BL/6 (B6) mice were given daily intraperitoneal injections of CsA (30 or 50 mg/kg) from day -1 and injected intravenously with alpha-GalCer (2 mug/mouse) on day 0.

Regulatory roles of NKT cells in the induction and maintenance of cyclophosphamide-induced tolerance.

We have previously reported the sequential mechanisms of cyclophosphamide (CP)-induced tolerance. Permanent acceptance of donor skin graft is readily induced in the MHC-matched and minor Ag-mismatched recipients after treatment with donor spleen cells and CP. In the present study, we have elucidated the roles of NKT cells in CP-induced skin allograft tolerance.

Sequential analysis of anti-alpha Gal natural antibody-producing B cells in GalT knockout mice in cyclophosphamide-induced tolerance.

Previously, we have shown that cyclophosphamide (CP)-induced tolerance, marked by permanent acceptance of donor skin graft and establishment of donor mixed chimerism, was readily induced with treatment with donor spleen cells (SC), CP, busulfan (BU) and donor bone marrow cells (BMC). Here, we investigated the mechanism of anti-donor natural antibody (nAb) producing B-cell tolerance in our CP-induced tolerance systems in alpha1,3-galactosyltransferase-deficient knockout mice (GalT KO; GalT-/-, H-2(b/d)). After induction of tolerance using donor AKR SC and BMC, survival of donor heart and skin grafts and production of anti-Galalpha1-3Galbeta1-4GlcNAc (anti-alphaGal) Ab in recipient GalT KO mice were analyzed.

The regulatory functions of Ly-49A, Ly-49D and Ly-49G2 on NK cells in the recognition and rejection of the alloantigen in vivo.

Ly-49A is an inhibitory receptor that binds H-2Dd and H-2Dk. The downregulation of Ly-49A is thought to mediate NK self tolerance in vivo. In this study, we analyzed the regulation of Ly-49A, D and G2 on NK cells in an in vivo rejection model.

Absent mRNA accumulation of Th1 or Th2 cytokines in heart allografts with chimerism-based drug-induced tolerance.

Purpose: We recently described using cyclophosphamide (CP) plus busulfan (BU) to create drug-induced skin and heart allograft tolerance capable of regularly overcoming fully H-2 mismatched barriers in mice. The present study investigates the intragraft mRNA expressions of Th1 and Th2 cytokines.

Methods: This method consists of the intravenous (i.

Requirement of a higher degree of chimerism for skin allograft tolerance in cyclophosphamide-induced tolerance.

By using a cyclophosphamide (CP)-induced tolerance system, we previously raised the possibility that the degree of chimerism might determine the induction of heart and skin allograft tolerance. When C3H (H-2k; Thy1.2, Mls-1b) mice were intravenously primed with 1 x 10(8) spleen cells (SCs) from H-2 matched AKR (H-2k; Thy1.

Effect of dietary anti-urease immunoglobulin Y on Helicobacter pylori infection in Mongolian gerbils.

Background And Aim: Helicobacter pylori is known to be a major pathogenic factor in the development of gastritis, peptic ulcer disease and gastric cancer. Recently, chicken egg yolk immunoglobulin Y (IgY) has been recognized as an inexpensive antibody source for passive immunization against gastrointestinal infections. The present study was designed to investigate the effect of anti-urease IgY on H.

Nigerooligosaccharides augments mitogen-induced proliferation and suppresses activation-induced apoptosis of human peripheral blood mononuclear cells.

Nigerooligosaccharides (NOS), a mixture of nigerose and nigerosylmaltooligosaccharides, consists of immunopotentiating oligosaccharides found in foodstuffs. We have previously reported that activation of peripheral blood mononuclear cells (PBMC) in response to concanavalin A (Con A) or a streptococcal preparation of OK-432 is augmented in healthy young adults and elderly subjects after the intake of NOS-supplemented syrup. A reappraisal of the data suggests that NOS augments proliferation but partly suppresses activation-induced apoptosis of PBMC in response to these mitogens.

The critical role of Fas-Fas ligand interaction in donor-specific transfusion-induced tolerance to H-Y antigen.

Background: Donor-specific transfusion (DST) has been clinically used to enhance the survival of transplanted organs, and it has been shown in mice to induce tolerance to male (H-Y) antigen (Ag). Although the biologic mechanisms that initiate and maintain DST-induced tolerance involve clonal deletion, induction of anergy, and generation of regulatory cells, the molecules essential to tolerance induction are still unclear. In this study, we investigated the role of Fas-FasL interaction in DST-induced tolerance to H-Y Ag.

Effects of Hochu-ekki-to and Ninjin-youei-to, traditional Japanese medicines, on porcine serum-induced liver fibrosis in rats.

In this study, we estimated the effects of traditional Japanese medicines on liver fibrosis in Wistar rats injected with porcine serum twice a week for 8 weeks. The rats were orally administered Hochu-ekki-to, Ninjin-youei-to (100 and 300 mg/kg/day) or Sho-saiko-to (300 mg/kg/day) 5 days per week. Serum and liver samples were obtained 2 days after the last porcine serum injection.

[Effect of PSK on Th1/Th2 balance in tumor-bearing mice].

We investigated the effect of PSK on Th1/Th2 balance in tumor-bearing mice. PSK was intraperitoneally administered to Meth A-bearing BALB/c mice, and PSK caused regression of the Meth A tumor. The results of Winn assay suggested that the effect of PSK was dependent on CD4+T cells.

Immune and non-immune factors in cryopreserved tissues.

Background: Although cryopreserved tissues are used clinically, the effects of cryopreservation on antigenicity leading to immune and non-immune responses are not well known.

Methods: We investigated the change of inflammatory effects of cryopreserved tissue by using spleen and aortic allografts from Class I antigen-disparate B6.C-H-2(bm1) (bm1; K(bm1), IA(b), D(b)), Class II antigen-disparate B6.

Suppressive effect of a traditional Japanese medicine, Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan), on the hyperresponsiveness to IL-18 in autoimmune MRL/MPJ-lpr/lpr mice.

Oral administration of Hachimi-jio-gan (HMG, Ba-Wei-Di-Huang-Wan), a traditional Japanese herbal medicine, for several weeks, ameliorates some autoimmune symptoms of MRL/lpr mice. In the short time treatment for 9 days, hyperresponsiveness of mesenteric lymph node (MLN) cells to interleukin (IL)-18 manifested by the proliferation or the production of interferon (IFN)-gamma was significantly suppressed. Additionally, the treatment with HMG suppressed the expressions of IL-18Ralpha and IL-18Rbeta mRNA in CD45R(-) T cells, and also the expression of IL-18Ralpha mRNA in unpurified whole cells.

Promotion of skin graft tolerance across MHC barriers by mobilization of dendritic cells in donor hemopoietic cell infusions.

Flt3 ligand (FL) dramatically increases the number of immunostimulatory dendritic cells (DC) and their precursors in bone marrow (BM) and secondary lymphoid tissues. Herein we tested the ability of FL-mobilized donor hemopoietic cells to promote induction of skin graft tolerance across full MHC barriers. C57BL/10 (B10; H2(b), IE(-)) mice were given 10(8) spleen cells (SC) from normal or FL-treated, H-2-mismatched B10.

Participation of contrasting changes in IL-10 and IL-12 production in the reduction of Th1-predominance by Hachimi-jio-gan in autoimmune MRL/MP-lpr/lpr mice.

Hachimi-jio-gan (Chinese name: Ba-Wei-Di-Huang-Wan, HMG), a traditional Japanese herbal medicine, has been used for disorders accompanying aging. Our previous studies suggested that HMG ameliorated Thl-predominant autoimmune diseases in MRL/lpr mice through inhibition of IL-12 production. In the present study, the oral administration of HMG down-regulated phosphorylated STAT4 and up-regulated phosphorylated STAT6 in CD4 T cells.

Crucial Fas-Fas ligand interaction in spontaneous acceptance of hepatic allografts in mice.

The Fas/Fas ligand (FasL) system plays important roles in the immune system, including host immunoregulation and cytotoxicity. In this study, we investigated the involvement of Fas-FasL interactions in spontaneous acceptance of hepatic allografts in murine orthotopic liver transplantation. Liver transplantation between the C57BL/6 (B6, H-2b) donor and the MRL/Mp (MRL, H-2k) recipient was performed in various combinations of donor and recipient mice with wild type (+/+), Fas-mutant (lpr) or FasL-mutant (gld) genotypes.

Mechanism of murine Vgamma1+ gamma delta T cell-mediated innate immune response against Listeria monocytogenes infection.

Murine gamma delta T cells participate in innate immune response against infection of the intracellular bacterium Listeria monocytogenes. In the present report, we analyzed the mechanism of the gamma delta T cell-mediated response against L. monocytogenes infection.

Heart allograft tolerance without development of posttransplant cardiac allograft vasculopathy in chimerism-based, drug-induced tolerance.

Background: Recently, we have described a drug (cyclophosphamide [CP] plus busulfan [BU])-induced skin allograft tolerance in mice that can regularly overcome fully H-2-mismatched barriers. Using this method, we have investigated whether or not this regimen can prolong the survival of heart allografts and inhibit the development of posttransplant cardiac allograft vasculopathy (CAV).

Methods: The components of the method are intravenous administration of 1 x 108 allogeneic spleen cells on day 0, intraperitoneal injection of 200 mg/kg of CP and 30 mg/kg of BU on day 2, and intravenous injection of T cell-depleted 1 x 107 allogeneic bone marrow cells from the same strain of mice on day 3.

The apoptotic protease-activating factor 1-mediated pathway of apoptosis is dispensable for negative selection of thymocytes.

Negative selection is a process to delete potentially autoreactive clones in developing thymocytes. Programmed cell death or apoptosis is thought to play an important role in this selection process. In this study, we investigated the role of apoptotic protease-activating factor 1 (Apaf1), a mammalian homologue of CED-4, in programmed cell death during the negative selection in thymus.

Calcineurin-dependent mitochondrial disturbances in calcium-induced apoptosis of human immunodeficiency virus gp160-expressing CD4+ cells.

In CD4+ UE160 cells with inducible expression of gp160, mechanisms of apoptosis induced by human immunodeficiency virus (HIV) Env protein were analyzed. Induction of gp160 caused intracellular calcium increase followed by the release of cytochrome c from mitochondria, which was inhibited by calcineurin inhibitors. Association of BAD with Bcl-xL was observed, and a portion of BAD was dephosphorylated after induction of gp160.