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Biomedical subjects

A Durandy

Publications and source records attributed to A Durandy.

At least 73 records · Page 4Linked to original sources

Immunosuppressive properties of synthetic peptides derived from CD4 and HLA-DR antigens.

Synthetic peptides derived from the beta 1 domain of HLA-DR antigens containing RFDS and a peptide derived from the immunoglobulin-like amino-terminal domain of CD4 and containing RADS were shown to exhibit specific dose-dependent inhibitory effects on antigen-induced HLA class II-restricted T-cell proliferation and in vitro antibody synthesis. These inhibitory activities are similar to those exhibited by anti-CD4 and HLA-DR antibodies, respectively. The peptides derived from HLA-DR or CD4 and anti-CD4 or anti-HLA-DR antibodies acted together in synergy to inhibit these responses when the relevant cell populations were incubated with infrainhibitory concentrations of the reagents. In contrast, these peptides were shown to exert no inhibitory activity on nonspecific T-cell activation mediated by ionomycin, phorbol myristate acetate, and interleukin-2.

Antibody Formation↗

The effect of RU 41740 on the in vitro maturation of human B-cells.

We have tested the effect of a Klebsiella pneumoniae extract, RU 41740, and its lipopolysaccharidic fraction (LPS-LAP) on the in vitro activation of human B-cells. Two models have been used: the polyclonal activation induced by pokeweed mitogen and the specific antibody production to mannan, a polysaccharide extracted from the cell wall of Candida albicans. We have shown that RU 41740, and especially its lipopolysaccharidic fraction, significantly increases the production of immunoglobulins and specific antibodies. This effect is mediated by T-lymphocytes, since preincubation of isolated T-cells, but not of non-T-cells, resulted in the same effect. Together with the known enhancing effect of LPS-LAP on T-cell proliferation, these data strongly suggest that LPS-LAP increases the production of B-cell-activating lymphokines by T-cells.

Adjuvants, Immunologic↗

Analysis of the membrane glycoproteins of platelets in the Wiskott-Aldrich syndrome.

We have examined the plasma membrane glycoproteins of platelets from three unrelated patients with the Wiskott-Aldrich syndrome. Single- or two-dimensional SDS-polyacrylamide gel electrophoresis was performed. Glycoproteins were located by staining for carbohydrate, or by autoradiography when the platelets had been surface-labelled with 125I prior to solubilization. In one patient a slight decrease in the 125I-labelling intensity of GP Ib, GP Ia and a 125I-labelled polypeptide of Mr 168,000 were noted. For the two other patients the glycoprotein profiles were indistinguishable from those of normal subjects. These results clearly indicate that abnormalities in platelet membrane glycoproteins are not a common trait among Wiskott-Aldrich patients, and thus cannot be regarded as primary defects in this disease.

Adolescent↗

Idiotypy of human anti-Candida albicans antibodies: recurrence, presence of a cross-reactive autoanti-idiotypic-like activity, and role in the induction of specific in vitro antibody response.

Rabbit anti-idiotypic antibodies (L12) were raised against human anti-mannan of Candida albicans (CA) antibodies isolated from the serum of a normal donor. The absorbed anti-idiotypic antiserum bound to donor anti-CA mannan antibodies but not to control immunoglobulins. Binding was inhibited by CA mannan but not by other polysaccharide antigens. L12 was shown to cross-react with anti-CA mannan-isolated antibodies or with anti-CA antibody-containing sera from individuals unrelated to the donor. IgG fraction isolated from the donor serum was repeatedly absorbed on CA mannan Sepharose to remove anti-mannan antibodies. This IgG fraction (named autoanti-idiotypic fraction) blocked, in a dose-dependent fashion, the binding of rabbit anti-idiotype to donor anti-CA mannan antibodies. Moreover, this CP-depleted IgG fraction cross-reacted with public idiotypic determinants of unrelated anti-CA mannan antibodies. Finally, L12 induced sensitized lymphocytes to produce anti-CA mannan antibodies in vitro in the absence of antigen.

Antibodies, Anti-Idiotypic↗

Prenatal diagnosis of severe combined immunodeficiency with defective synthesis of HLA molecules.

The immunodeficiency associated with a defective expression of HLA molecules is an autosomal recessive disorder leading to death during childhood. We have performed prenatal diagnosis for six fetuses at risk for this disease by membrane immunofluorescence on blood lymphocytes and monocytes, using specific monoclonal antibodies for HLA class I and II molecules. Two pregnancies have been found to be affected. The diagnosis has been confirmed on each abortus by the study of the membrane expression of HLA class I and II molecules on blood lymphocytes and monocytes, and on thymic and splenic cells. The four other cases were found to be normal both during pregnancy and after birth. The detection of the defect as early as the 20th week of gestation allows selective termination.

Female↗

Prenatal diagnosis of chronic granulomatous disease (CGD) in four high risk male fetuses.

Prenatal diagnosis of chronic granulomatous disease (CGD) was performed in four male high risk fetuses. The male sex was previously determined by an amniotic cell karyotype. Three kinds of test were performed on fetal blood obtained by umbilical venous puncture under fetoscopy at the 20th gestational week: nitroblue tetrazolium reduction (NBT) cytochemical test with phorbol myristate acetate (PMA) as activator; luminol enhanced chemiluminescence with activation by serum opsonized zymosan (STZ) or PMA; superoxide anion (0-2) production by measurement of the superoxide dismutase inhibitable reduction of cytochrome c with PMA as activator. Results were compared to those obtained in six fetuses investigated for other inherited diseases. In one case, absence of granulocyte defects was confirmed at birth. In three other cases, the tests showed deficient metabolic oxidative granulocytes. The pregnancy was terminated and the CGD diagnosis was confirmed on the products of abortion. The use of three different techniques performed on whole blood for CGD prenatal diagnosis is recommended instead of a single isolated test to ensure a higher confidence in the diagnosis.

Female↗

Mannan-specific and mannan-induced T-cell suppressive activity in patients with chronic mucocutaneous candidiasis.

We have studied T- and B-cell responses to antigens of Candida albicans in 18 patients suffering from chronic mucocutaneous candidiasis. We have shown that in vitro production of antibody to one of these antigens, mannan, was absent during the active phase of the disease and that this absence was consequent to the activation of specific CD8(+) and CD8(-) suppressor T lymphocytes. Such activation was also observed when control T lymphocytes were incubated in the presence of monocytes and a high concentration of mannan. This suppressive effect was specific to antigens of Candida albicans, was radiosensitive, and was not consequent to the secretion of prostaglandin E2. It appeared as well that the induction of these suppressor T cells was HLA-DQ restricted. The suppressor T-cell activity induced by antigens of Candida albicans in vitro is thus comparable to the suppressor T-cell activity observed in vivo in patients affected with chronic mucocutaneous candidiasis. Defective handling of mannan by monocytes could result in the accumulation of mannan, resulting in the activation of specific T suppressor cells and in the consequent cellular immunodeficiency specific to Candida albicans. Successful treatment of the candidiasis resulted in complete correction of the immune abnormalities.

Adolescent↗

Glomerulonephritis, B monoclonal small lymphocytic lymphoma and mixed cryoglobulinemia.

A novel association in the same patient with small lymphocytic lymphoma, type II cryoglobulinemia and glomerulonephritis is reported. This case is also characterized by a quite unusual sequence of glomerular alterations. A first renal biopsy showed severe endocapillary proliferative glomerulonephritis due to monocytic infiltration without any evidence of deposition of immune reactants. The immune deposits associated with type II cryoglobulinemia were only observed at a second renal biopsy performed five months later. This case shows that mononuclear cells can be responsible in and of themselves for severe glomerular damage, without deposition of immune material, and suggests that monocytic infiltration might be the first stage of type II cryoglobulinemia associated glomerulonephritis.

B-Lymphocytes↗

Role of the LFA-1 molecule in cellular interactions required for antibody production in humans.

The lymphocyte function-associated antigen 1 (LFA-1) has been shown to play a role in various T cell functions in mice and humans including cytotoxicity, and proliferation to allogeneic cells and foreign antigens. These functions have been defined with specific monoclonal antibodies and were additionally confirmed by the investigation of patients with inherited deficiency in membrane LFA-1 expression. In this paper, we report our studies on the potential role of the LFA-1 molecule in T lymphocyte-dependent antibody responses. In a patient with a complete lack of membrane expression of LFA-1, there was no in vivo antibody response to vaccinal antigens such as tetanus, diphtheria toxoids, and polio virus, and no in vivo or in vitro antibody production to influenza virus, whereas serum immunoglobulin levels and antibodies to polysaccharides (isohemagglutinins, antibody to mannan, and a polysaccharide from Candida albicans) were detected in correlation with in vitro production of anti-mannan antibody. The defective antibody response to polypeptides was not secondary to poor antigen-specific T proliferation, because the latter was found to be present. Similarly, in vitro antibody production to influenza virus of normal cells was blocked by several anti LFA-1 monoclonal antibodies specific for the alpha subunit of the molecule, if they were added from the beginning of the culture. The antibody production blockade could be achieved with monoclonal antibody concentrations that partially preserved T cell proliferation. The helper effect of an influenza virus-specific helper T cell clone was also blocked. The targets of the blockade were shown by incubation experiments to be T cells and monocytes. In contrast, anti-LFA-1 monoclonal antibodies had no effect on pokeweed mitogen-induced B cell maturation into immunoglobulin-containing cells and on the anti-mannan antibody production. These combined data demonstrate that the LFA-1 molecule plays a role in T cell dependent antibody production to polypeptidic antigens but not in the antibody response to polysaccharides, although the antibody response to mannan is T cell dependent. It is proposed that the LFA-1 molecule is required to some extent for a antigen-presenting cells-T lymphocyte interaction and for the maintenance of a close association between antigen-specific helper T cells and small resting B lymphocytes. Polysaccharidic antigens that exhibit repetitive antigenic determinants might cross-link membrane immunoglobulins on B lymphocytes, thus allowing B cells to pass through a first step of activation requiring cognate T-B cell interaction.

Antibodies, Monoclonal↗

Possible T4-HLA class II interaction as an essential event in antigen-specific helper T lymphocyte-dependent B cell activation.

We have previously shown that the interaction between influenza virus-specific helper T lymphocytes and B lymphocytes is HLA class II restricted (Fischer, A. et al., Eur. J. Immunol. 1985. 15: 620). In the present study, we used a panel of antibodies specific for the T4 and HLA-DR molecules to investigate the role of both structures in T-B lymphocyte interaction. Several anti-T4 monoclonal antibodies were shown to block the in vitro antibody production to A/Bangkok influenza virus while they were unable to inhibit the A/Bangkok-induced proliferation of specific helper T cell clones. Some anti-HLA-DR monoclonal antibodies inhibited the antibody production to A/Bangkok, the target of the inhibition being either monocytes or B lymphocytes. The incubation of helper T cell clones with an infra-inhibitory concentration of anti-T4 antibody and of B lymphocytes with an infra-inhibitory concentration of anti-HLA-DR antibody resulted in a mutual enhancement of inhibition. Such synergistic interactions were not observed using combinations of anti-T4 and anti-B membrane structures such as p35 or LFA-1 or anti-HLA-DR and anti-T membrane structures such as T11 or LFA-1. First, these results indicate that the T4 molecule plays an essential role in T-B cell interaction even when it is not absolutely required for T cell proliferation. Second, they strongly suggest that the T4 molecule directly interacts with HLA-DR at the B cell surface. Whether such interaction is required to enhance the stability of T3/T cell receptor-antigen plus HLA class II association or whether T4-HLA-DR may transduce a signal towards B lymphocytes that is required in B cell activation remains unknown.

Antibodies, Monoclonal↗

Impaired T8 lymphocyte-mediated suppressive activity in patients with partial Di George syndrome.

We have studied the in vitro B-cell maturation induced by pokeweed mitogen of lymphocytes from seventeen patients with partial Di George syndrome. These patients were characterized by a low number of T8(+) lymphocytes. They had normal immune functions with an increased level of serum IgE for most of them. These patients were investigated before the age of 1 month. In contrast to age-matched subjects, their lymphocytes were able to produce in vitro immunoglobulins, although the level of immunoglobulin production was lower than in adults. These data were explained by a lack of T-cell mediated suppressor activity normally found in newborns. There was a strong correlation between the low number of T8(+) lymphocytes and the magnitude of the in vitro immunoglobulin production by patients' cells. This was further demonstrated by the ability of residual T8(+) lymphocytes isolated from patients to normally suppress the PWM driven B cell maturation on a per cell basis. The defective T-cell mediated suppression progressively disappears within 5 months. It is possible that this phenomenon is secondary to a delayed differentiation of suppressor T-cells in patients with partial Di George syndrome.

Antigens, Surface↗

Restriction of the in vitro anti-mannan antibody response by HLA-DQ molecules.

In humans, the in vitro antibody response directed towards mannan, a polysaccharide extracted from the cell wall of Candida albicans, has been previously shown to be dependent on the presence of T lymphocytes and monocytes. Evidence is now given for the existence of a genetic restriction governing this response since antibody production is achieved provided that monocytes and T lymphocytes on one side and monocytes and B lymphocytes on the other side are of the same origin. In order to delineate the restriction element governing these interactions, blocking experiments have been designed using well-defined monoclonal antibody, anti-HLA class II molecules. The results clearly indicate that the restriction element belongs to the HLA-DQ molecular series, as shown in T-cell proliferation and antibody production assays in the presence of either T cells or T-cell supernatants. Incubation of isolated cell populations (T, B lymphocytes and monocytes) with the monoclonal antibody have indicated that DQ determinants are involved in the mannan presentation by monocytes to T and B cells. The HLA-DQ mediated restriction of the in vitro immune response to mannan has been observed in all the subjects tested, suggesting that mannan epitopes are preferentially, or even only, recognized in association with an unique group of HLA-class II molecules, namely HLA-DQ.

Antibodies, Monoclonal↗

Specific binding of antigen onto human T lymphocytes.

Human T lymphocytes sensitized to Candida albicans (CA) were shown to proliferate in cultures induced with mannan, a ramified polysaccharide extracted from the cell well of CA. We presently describe that, when we used strongly labeled [3H]mannan, antigen-specific T blast cells were able to bind the labeled mannan on their membrane. The observations that irrelevant blast cells did not bind [3H]mannan, and that mannan-specific blast cells did not bind tritiated pneumococcal polysaccharide SIII, indicate the specificity of mannan binding. Mannan binding was reversible and saturable. Mannan binding on T blast cells was inhibited by preincubation with monoclonal antibodies to T3 but not to other T cell-related molecules. The characteristics of this receptor suggest its identity with the T cell receptor for antigen. The direct binding of mannan could be either due to a cross-linking of the receptor by multivalent mannan or to a recognition of mannan in association with HLA-DQ molecules, as suggested by partial blocking of mannan binding using anti-HLA-DQ monoclonal antibodies.

Adult↗

HLA-haploidentical bone marrow transplantation for severe combined immunodeficiency using E rosette fractionation and cyclosporine.

Eight patients with severe combined immunodeficiency received bone marrow cells from their HLA haplotype-identical fathers after bone marrow T cell depletion by rosetting with neuraminidase-treated sheep red cells. Because the method led to the infusion of a small percentage of T lymphocytes (0.1% to 0.3%), cyclosporin was given by continuous intravenous infusion for two months in order to prevent the occurrence of graft-v-host disease (GVHD). Three patients who did have residual nonfunctional T lymphocytes received busulfan and cyclophosphamide before transplantation. Engraftment was observed in seven patients, and severe GVHD was not seen. Two patients died early after the bone marrow transplantation because of prior infections, and a third died at day 90 from a B cell lymphoproliferative syndrome. The five other patients are doing well. Stable engraftment has been achieved with reconstitution of cell-mediated immunity in 5/5 and humoral immunity in 4/5 patients.

Adenosine Deaminase↗