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H Bazin

Publications and source records attributed to H Bazin.

At least 55 records · Page 3Linked to original sources
PubMed1997

Administration of exogenous interleukin-2 abrogates spontaneous rat liver allograft acceptance but does not affect long-term established graft survival.

BACKGROUND: Spontaneous tolerance to the orthotopic liver allograft uniformly occurs in the DA (RT1a) to PVG (RT1c) rat combination despite a fully allogeneic barrier. METHODS: To assess whether spontaneous acceptance might be the consequence of a T cell help deficit at the time of the first exposure of alloantigens to the host, we studied the effect of exogenous interleukin (IL)-2 injections at the time of liver transplantation and during long-term follow-up. RESULTS: Although spontaneous acceptance of the liver allograft constantly ensued in the DA to PVG combination, a daily injection of recombinant IL-2 (3 x 10(5) U) uniformly provoked acute cellular rejection of the liver allograft and consequently the death of animals by postoperative day 5-6. Simultaneous to the graft loss, hepatic enzymes (alanine aminotransferase) increased more than 50-fold in IL-2-treated recipients, whereas similar IL-2 treatment did not produce any hepatic dysfunction in syngeneic animals. By immunohistology, the expression of the alpha chain of the IL-2 receptor, usually undetectable in untreated animals, was evident on CD4 and CD8 lymphocytes infiltrating the liver graft. In contrast, a similar IL-2 regimen and even higher IL-2 doses (x 10(6) U) did not abrogate the liver allograft survival during long-term follow-up. CONCLUSIONS: Our results demonstrate that spontaneous rat liver allograft acceptance may be abolished by exogenous IL-2 injections, which suggests that an "inherent T cell help deficit" might be implicated in the spontaneous acceptance mechanisms of DA to PVG liver allografts.

Alanine Transaminase↗
PubMed1997

Studies on the mechanisms involved in antigen-evoked pleural inflammation in rats: contribution of IgE and complement.

Immunoglobulin E (IgE) has been shown to play a critical role in the allergic late-phase reaction, which is marked by intense leukocyte infiltration and edema. In this study we assessed the allergic pleural inflammation triggered by intrapleural (i.pl.) challenge in sensitized rats. We examined pleural effluent from actively sensitized rats following anti-IgE monoclonal antibody (mAb) (MARE-1) provocation for protein exudation, neutrophil as well as eosinophil accumulation. Inflammatory changes triggered by antigen after passive sensitization with IgE mAb was also assessed for comparison. Total serum level of IgE was found to be about threefold increased 7-8 days post-active sensitization, remaining augmented for at least 30 days. Increased levels of peritoneal leukocyte-bound IgE and serum IgE with specificity to ovalbumin were also detected. Nevertheless, the anti-IgE challenge in 14-day actively sensitized was shown to be a weak stimulus of neutrophil and eosinophil accumulation, despite being able to cause intense protein extravasation. Similarly, antigen challenge of IgE-passively sensitized rats caused protein leakage that was comparable to that induced by anti-IgE mAb in actively sensitized rats but led to a much lower neutrophil/eosinophil infiltration. Also, blockade of complement with recombinant human soluble C receptor-1 (sCR1) treatment prevented actively sensitized rats from reacting to antigen with neutrophil and eosinophil recruitment without modifying protein extravasation. These data suggest that IgE and complement-mediated mechanisms probably account for the exudation and leukocyte infiltration that is characteristic of the pleural inflammatory response observed in actively sensitized rats.

Aluminum Chloride↗
PubMed1997

Neutralization of bothropic and crotalic venom toxic activities by IgG(T) and IgGa subclasses isolated from immune horse serum.

IgG(T) and IgGa isotypes were isolated from horse hyperimmune anti-bothropic and anti-crotalic sera using a combination of two affinity chromatographic processes. IgG(T) and IgGa isotypes were isolated from these sera by chromatography on protein A-Sepharose followed by separation of the two isotypes by chromatography on a column of anti-IgG(T)-Sepharose. LO-HoGT-1, a rat anti-horse IgG(T) monoclonal antibody, was used. A comparative study of the efficiency of these isotypes in neutralizing the main toxic activities of the homologous venoms was carried out. It was found that IgG(T) was about three-fold and seven-fold more protective than IgGa for neutralization of the lethal activity of B. jararaca and C. d. terrificus venoms, respectively. IgG(T) was also more effective than IgGa for the neutralization of the haemorrhagic activity induced by B. jararaca venom, while both isotypes neutralized equally well the blood incoagulability induced by this venom. The results suggest that IgG(T) is the most protective isotype present in both anti-bothropic and anti-crotalic sera, followed by IgGa. Owing to their very low concentration in the serum, other IgG isotypes are not likely to be important in neutralizing the venoms' toxic activities.

Animals↗
PubMed1996

A new and simple method to study the role of soluble factors in antibody-mediated cell modulation.

This paper describes an in vitro method to study how interactions between cell suspensions incubated in two culture compartments can occur by diffusion of small molecules through a dialysis membrane. This consists of in vitro cultures of a human PBMC suspension, divided into two parts separated by a dialysis membrane. In one of the cultures, a mitogenic monoclonal antibody (mAb) is added. The porosity of the membrane permits cytokines secreted by activated cells to pass while blocking the antibodies. As a model, PBMC from the same blood donor were divided into two parts and one portion was incubated with an anti-CD3 monoclonal antibody (OKT3 Ortho-Cilag), known to induce IL-2 secretion whereas the other was enclosed in a dialysis bag without antibody. After a 4 day incubation, the cells incubated outside the bag proliferate and secrete cytokines which pass through the membrane and induce cell proliferation inside the bag. This method could complement the currently used methods for the analysis of antibody-mediated cell activation.

Animals↗
PubMed1996

Prophylactic immunosuppression with anti-interleukin-2 receptor monoclonal antibody LO-Tact-1 versus OKT3 in liver allografting. A two-year follow-up study.

A prospective trial was conducted in 129 recipients of primary liver transplantation, to compare induction immunosuppression using triple drug therapy (cyclosporine, steroids, and azathioprine; group 1, n = 42), versus triple drug therapy with a 10-day course of OKT3 (group 2, n = 44) or of the anti-interleukin-2 receptor monoclonal antibody LO-Tact-1 (group 3, n = 43). Two-year actual patient survival rates were 64%, 79%, and 93% in groups 1, 2, and 3, respectively (1 vs. 2, NS; I vs. III, P = 0.003; 2 vs. 3, NS). Up to 2 years after transplantation, 18%, 44%, and 53% of the grafts in groups 1, 2, and 3, respectively, had not experienced steroid-resistant acute rejection (1 vs. 2, P = 0.002; 1 vs. 3, P = 0.007; 2 vs. 3, NS). The overall incidence of chronic rejection was 4%. OKT3 therapy, but not LO-Tact-1, significantly increased the incidence of cytomegalovirus infections (P = 0.019). In conclusion, immunoprophylaxis with LO-Tact-1 seemed to provide a liver graft acceptance rate at least as satisfactory as that with OKT3, without an increase in the incidence of infections.

Antibodies, Monoclonal↗
PubMed1996

Modulation of rat B cell differentiation in vivo by the administration of an anti-mu monoclonal antibody.

We have previously described that the administration of an anti-mu mAb to adult rats results in the total depletion of circulating IgM. In the present study we analyzed the cellular mechanisms involved in the depletion of circulating IgM by the administration of an anti-mu mAb to adult rats. Administration of an anti-mu mAb to adult rats led to the cross-linking and internalization of membrane IgM (mIgM) but not mIgD on the surface of B cells. This correlated with the depletion in spleen and bone marrow of immature and short-lived Thy-1+ CD45RB+ B cells and with the specific depletion of the number of IgM but not IgA-, IgG1-, IgG2a-, and IgG2b-secreting cells in the spleen, which paralleled the depletion of circulating IgM but not IgA, IgG1, IgG2a, and IgG2b. In contrast to the other IgG subclasses, IgG2c-secreting cells as well as circulating IgG2c were increased by 10-fold in anti-mu-treated rats as compared with controls. Finally, anti-mu-treated rats showed an inhibition in the generation of primary thymus-dependent as well as thymus-independent Ab responses as compared with controls. In conclusion, the data presented suggests that anti-mu administration in adult rats results in the early arrest of B cell differentiation in the bone marrow, which causes the down-regulation of IgM production. Furthermore, anti-mu mAb administration directly or indirectly activates a particular subset of mature B cells, which differentiates into IgG2c-secreting cells.

Animals↗
PubMed1996

Biodistribution of iodine-125 tyramine transforming growth factor alpha antisense oligonucleotide in athymic mice with a human mammary tumour xenograft following intratumoral injection.

The Watson-Crick base pairing rule provides the underlying principle for the antisense (AS) approach to inhibiting gene expression. Transforming growth factor alpha (TGFalpha) was the first growth factor to be associated with tumorigenesis, thus making the TGFalpha (mRNA) a potential target for AS therapy and offering the potential for monitoring of the progression of malignancy by non-invasive imaging with radiolabelled AS phosphodiester. Probe labelling and biodistribution were studied in the present report. A 23-mer oligonucleotide sequence was synthesized and grafted in 5' with a tyramine group which was further radioiodinated. The radiolabelled AS was injected intratumorally in mammary tumour-bearing BALB/c mice (3 weeks after inoculation of 7.10(6)NS2T2A mammary cells). Biodistribution was monitored by sequential scintigraphy and organ radioactivity after autopsy. The 5' tyramine group allowed specific and stable radiolabelling of the AS with 125I. The 125I AS oligonucleotide was rapidly cleared from the tumour by intestine and kidneys. Four hours after intratumoral injection, 6.5%+/-1.5% of the dose was retained in the tumour as non-degraded 125I AS. It is concluded that 5' tyraminylated AS provides information on the biodistribution of AS oligonucleotide following intratumoral injection. These data will contribute to the pharmacology of AS oligonucleotides which can be used for therapy.

Abdomen↗
PubMed1996

A promising model of primary human immunization in human-scid mouse.

The engraftment of human peripheral blood mononuclear cells (Hu-PBMC) from adult donors in scid mice has been published by MOSIER et al. in 1988. The possibility to obtain a secondary human immune response in human-scid mice has also been reported but attempts to induce a primary human immune response still remain difficult to achieve. In this work, an antigen (Canine albumin) or a hapten (DNP) was coupled with tetanus toxoid, an antigenic protein against which our human donors already had memory T cells through vaccination. In this way, hu-scid mice immunized with coupled DNP-tetanus toxoid (TT-DNP) or coupled Canine albumin-Tetanus toxoid (Calb-TT) mounted a specific human immune response anti-DNP or anti-Canine albumin (Calb) respectively. A secondary human immune response anti-tetanus toxoid was also detected in the sera of hu-scid mice immunized with product containing TT but not in the sera of those injected with PBS alone. The scid mice grafted with Hu-PBMC from a TT naive donor and challenged with Calb-TT or Calb alone failed to produce specific anti-Calb antibodies. These observations demonstrate that memory T cells can give a substantial help to naive B cells which interact with them for obvious B cell activation and differentiation into plasma cells. This model of immunization might be useful for other antigens of choice, allowing the production of human monoclonal antibodies, in combination with a suitable system of immortalization. Attempts to immunize human cells in scid mice against DNP coupled to LO-BM2 (a rat monoclonal antibody anti-human IgM) failed to induce a specific human response either anti-rat immunoglobulins (Igs), or anti-DNP and led to a decrease of human Ig production in hu-scid. We also immunized hu-scid mice against ovalbumin alone but, only in some cases, a low specific human immune response was observed, so this system seems to be unreliable.

Animals↗
PubMed1996

Human recombinant interleukin-4 (HurIL-4) improves SCID mouse reconstitution with human peripheral blood lymphocytes.

The application of human-scid mouse chimera (hu-scid) technology has some limitations, because of the variable amounts and functional heterogeneity of human cells recovered from engrafted mice. Attempts to optimize the construction of hu-scid chimeras with human peripheral blood mononuclear cells (Hu-PBMC) by using in vivo anti-asialo GM1 antibody treatment in mice in order to eliminate natural killer cells have been published by other authors with interesting results. In this study, Hu-PBMC were incubated in vitro with human recombinant interleukin-4 (HurIL-4) or human recombinant interleukin-2 (HurIL-2) for two hours and were intraperitoneally transferred into scid mice. Total human IgM and IgG levels in hu-scid sera, human cell markers in the thymus and in the spleen of grafted mice were considered as parameters of successful engraftment. HurIL-4 significantly enhanced human immunoglobulin production while HurIL-2 did not show any obvious effect. Human cell markers (CD2 and CD19) were significantly higher in the group of HurIL-4 treated Hu-PBMC than in the other groups, despite the high variability in human cell proliferation in the recipients. Thus, HurIL-4 can be used as an adjuvant growth factor which improves successful engraftment of human peripheral blood lymphocytes in scid mice.

Animals↗
PubMed1996

Vanin-1, a novel GPI-linked perivascular molecule involved in thymus homing.

Migration of hematopoietic precursor cells to the thymus is shown to depend upon a novel molecule called Vanin-1 expressed by perivascular thymic stromal cells. An anti-Vanin-1 antibody blocks the binding of pro-T cells to thymic sections in vitro, the in vivo accumulation of bone marrow cells around cortical thymic vessels, and long-term thymic regeneration. Thus, it interferes with the entry, and not the differentiation, of hematopoietic precursor cells. The Vanin-1 gene codes for a GPI-anchored 70 kDa protein that shows homology only with human biotinidase. Transfection of thymic stromal cells with the Vanin-1 cDNA enhances thymocyte adhesion in vitro. These data suggest that Vanin-1 regulates late adhesion steps of thymus homing under physiological, noninflammatory conditions.

Amidohydrolases↗
PubMed1996

An anti-CD2 mAb induces immunosuppression and hyporesponsiveness of CD2+ human T cells in vitro.

We describe here the potent specific immunosuppression obtained in vitro by LO-CD2a, a rat mAb directed against the human CD2 molecule. Addition of low dose LO-CD2a (40 ng/ml) at the time of mixed lymphocyte culture (MLC) initiation inhibits 80% of the proliferation and, more impressive, addition of the mAb 4 days after culture initiation at a similar concentration still suppresses 50% of the MLC. When responder T cells previously treated with LO-CD2a are challenged a second time by the same donor or third party allogeneic cells, hyporesponsiveness occurs in both cases, although reactivity to T cell mitogenic stimulation persists. Finally, the low production of cytokines such as tumor necrosis factor-alpha and IFN-gamma after incubation of human T cells with LO-CD2a suggests the absence of T cell activation. These results demonstrate that LO-CD2a mAb has a significant immunosuppressive effect and induces hyporesponsiveness in vitro, thereby suggesting potential efficacy in vivo for the treatment of acute rejection and for the induction of tolerance in allotransplantation.

Antibodies, Monoclonal↗
PubMed1996

In vivo interleukin-4 regulation of antibody responses in euthymic and athymic mice to a T-independent antigen (hydroxyethyl starch).

The aim of this work was to analyze the implication of IL-4 in the antibody response induced in vivo after immunization with a class II T-cell-independent (TI) antigen. IL-4 suppression, through administration of a rat monoclonal antibody antimurine IL-4 (11B11), in euthymic BALB/c mice during the course of immunization with the DNP-coupled hydroxyethyl starch (TI antigen), inhibited the production of anti-DNP IgG1 antibodies, potentiated the synthesis of IgG2a and had no effect on the other isotypes (IgM, IgG2b and IgG3). After IL-4 treatment of athymic BALB/c mice in the same conditions, although the IgG2a production was not increased, the IgG1 synthesis was significantly decreased, as was observed in euthymic mice. These results demonstrate that cytokine IL-4 plays an active role in vivo in the regulation of antibody response after immunization by a T-cell-independent antigen, in normal as well as in nude mice. The origin of IL-4 in these animals and especially in those athymic mice remains to be determined.

Animals↗
PubMed1995

Lack of L-selectin expression by cells transferring diabetes in NOD mice: insights into the mechanisms involved in diabetes prevention by Mel-14 antibody treatment.

The process of mononuclear cell extravasation from the blood into the islets of Langerhans in nonobese diabetic (NOD) mice is dependent on the expression of a set of molecules, most of which remain to be defined. The observation that vascular addressins are expressed in inflamed islets raises the issue of the involvement of one of their ligands, L-selectin, in the pathogenesis of autoimmune diabetes. Treatment of NOD females with Mel-14, an antibody specific for L-selectin, reduced the spontaneous development of both insulitis and diabetes. Pretreatment of diabetic donors with Mel-14 decreased the capacity of their splenocytes to transfer the disease. However, the treatment of recipients had no effect on the transfer of diabetes by untreated diabetogenic splenocytes. To reconcile these apparently conflicting results, we fractionated spleen T cells from diabetic mice according to L-selectin expression. Diabetogenic cells were found only in the L-selectin subpopulation. Thus, diabetogenic cells in adult mice share phenotypic characteristics with activated/memory cells, and enter the pancreas using L-selectin-independent migratory pathways.

Animals↗