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Biomedical subjects

A Durandy

Publications and source records attributed to A Durandy.

At least 91 records · Page 5Linked to original sources
PubMed1985

Genotyping with DNA probes in combined immunodeficiency syndrome with defective expression of HLA.

We performed HLA genotyping by using restriction-enzyme fragments hybridized with specific HLA probes instead of traditional immunologic methods in two patients whose lymphocytes expressed so few HLA antigens on the cell surface that serologic methods failed. Segregation of restriction-fragment-length polymorphism permitted identification of the genotypes. In addition, known correlations between serologically determined antigens and restriction-fragment-length polymorphism were confirmed. We applied this approach in making therapeutic decisions regarding bone marrow transplantation.

Bone Marrow Transplantation↗
PubMed1985

HLA class II restriction governing cell cooperation between antigen-specific helper T lymphocytes, B lymphocytes and monocytes for in vitro antibody production to influenza virus.

To study HLA class II compatibility requirement for in vitro antibody production to influenza virus, semipurified T lymphocytes, B lymphocytes and monocytes from HLA-typed responder donors were used. The presence of the three subpopulations was required for antibody production while a mixture of only two of those was ineffective. When using fresh T lymphocytes which exert an allogeneic suppressive effect and may also exhibit allogeneic helper activity, it was not possible to conclude an HLA class II-linked restriction of T-B cell cooperation although there was a suggestion of it. However, a grown H3 hemagglutinin-specific T cell line (L2), previously shown to be restricted by HLA-DR molecule (DR1) for interaction with antigen-presenting cells and devoid of allogeneic reactivity, exerts an HLA class II-restricted helper activity. This was demonstrated by various combinations of HLA-DR semi-compatible or incompatible B lymphocytes and/or monocytes with L2 T cells. The restriction element was identified as an HLA-DR determined since HLA-DC-compatible, HLA-DR-incompatible B lymphocytes were not helped by L2 T cells. In addition, monoclonal anti-HLA-DR but not anti-HLA-DC antibodies directed to the relevant specificity did inhibit the antigen-specific helper activity. We present evidence that not only T monocyte but also T-B and/or T-B-monocyte interactions are HLA class II restricted.

Antibodies, Viral↗
PubMed1985

The effects of indomethacin administration during pregnancy on women's and newborns' T-suppressor lymphocyte activity and on HLA class II expression by newborns' leukocytes.

It has been previously shown that T lymphocytes from human newborns and pregnant women exert a suppressive activity when assayed on the PWM-induced B cell maturation. The mechanisms of the suppression have remained entirely unknown. Prostaglandin E2, known to trigger T-cell mediated suppressive activity, may be involved. We took advantage of the treatment of pregnant women with indomethacin, because of premature labor or hydramnios, to investigate the role of prostaglandins in the activation of T suppressor (TS) activity. Administration of indomethacin (250 mg/day for 1-7 weeks, then 150 mg/day for 3-12 weeks) during the third trimester of pregnancy, abrogated the TS activity in the nine women and the three newborns tested. Abrogation of TS activity by indomethacin therapy led to normal PWM-induced B cell maturation in pregnant women but not in newborns. Moreover, the low expression of HLA class II antigens observed on normal newborn B lymphocytes and monocytes was corrected in newborns from indomethacin-treated mothers. Our results strongly suggest that prostaglandins may play a role in induction of TS activity observed in normal pregnant women and newborns and in the decreased expression of HLA class II antigens on newborns' leucocytes. Both phenomena could play a role in immunological interactions between mother and fetus.

B-Lymphocytes↗
PubMed1985

A defect in the regulation of major histocompatibility complex class II gene expression in human HLA-DR negative lymphocytes from patients with combined immunodeficiency syndrome.

Patients with an autosomal recessive combined immunodeficiency are characterized by an HLA negative phenotype of activated T and B lymphocytes. To determine the molecular basis of this syndrome we have studied the biosynthesis of class I and II antigens and the expression of relevant genes in these patients. The synthesis of the HLA A, B, and C heavy chain is markedly decreased, while beta 2 microglobulin is made in normal amounts. Biosynthesis of HLA-DR alpha-chain and beta-chain is abolished in the lymphocytes of these patients and there is a total absence of mRNA for either alpha-chains or beta-chains of HLA-DR. This indicates that the lack of class II antigen on these lymphocytes results from a block in the expression of HLA-DR genes. The Ii-chain, the invariant polypeptide associated intracellularly with HLA-DR, and its mRNA are made in normal amounts. Since the structural genes coding for class II polypeptides do not seem to be affected, the reported genetic defect in the patients concerns the regulation of the expression of HLA-DR genes.

Antigens, Surface↗
PubMed1985

Deficiency of the adhesive protein complex lymphocyte function antigen 1, complement receptor type 3, glycoprotein p150,95 in a girl with recurrent bacterial infections. Effects on phagocytic cells and lymphocyte functions.

A patient presenting delayed umbilical cord detachment, severe recurrent bacterial infections, and inability to form pus exhibited a profound defect in the expression of alpha- and beta-chains of the receptor for the C3bi fragment of C3 (CR3), lymphocyte function antigen 1 (LFA-1) molecule, and the p150,95 molecule found on neutrophils, monocytes, and lymphocyte membranes. This was shown by immunofluorescence studies using specific monoclonal antibodies, rosette formation with C3bi-coated erythrocytes, and immunoprecipitation for the LFA-1 complex. These membrane defects were responsible for abnormal phagocytic cell functions including adherence to nylon wool, cell movement, phagocytosis, and opsonized particle-induced oxidative response and for defective natural killer cell activity. In addition, lymphocyte function deficiencies previously unobserved in this disease were found. Cytolytic T lymphocyte activity was profoundly reduced; alpha- and gamma-interferon production were impaired. Finally, there was no antibody production to vaccinal antigens whereas the antibody responses to polysaccharides and to cytomegalovirus were found to be normal. The cytotoxic T cell deficiency could be expected from previous blocking experiments of this function with monoclonal antibodies to LFA-1 and is probably related to an extremely severe deficiency in LFA-1 expression in this patient. Anomalies in interferon and in antibody production suggest additional role(s) of the LFA-1 complex in monocyte/T lymphocyte/B lymphocyte cell interactions that have not yet been envisaged.

Antibodies, Monoclonal↗
PubMed1985

Separation of a population of human T lymphocytes that bind prostaglandin E2 and exert a suppressor activity.

Prostaglandin E2 (PGE2) is a potent inhibitor of immune functions. Two possible mechanisms of PGE2-mediated suppression have been proposed: one is a direct inhibitory effect exerted on interleukin 2-producing T cells; the second is mediated by the activation of nonspecific suppressor T lymphocytes. We previously showed that PGE2 can directly activate human T lymphocytes to suppress lymphocyte proliferation and B lymphocyte maturation. Herein is described the binding of 10 to 30% of human peripheral blood T lymphocytes to insolubilized PGE2 coated to albumin-Sepharose. The T lymphocytes that bound PGE2 (PGE2(+] could be eluted by the addition of serum and gentle shaking of the beads. The following data indicated the specificity of the binding: i) T lymphocytes after an overnight incubation, a condition known to abolish sensitivity to PGE2, lost their affinity for PGE2; ii) preincubation of T lymphocytes with PGE2 blocked the binding; iii) PGE2(+) T cells bound PGE after a 24-hr incubation, whereas PGE2(-) T cells did not. Few T cells bound albumin, and only a small percentage (7 to 9%) bound 6-keto-prostaglandin F1 alpha-coated beads. Among PGE2(+) T cells, there was a slight increase in the percentage of OKT8+ cells. Although T cells that had no affinity for PGE2 (PGE2(-] proliferated as well as unseparated T lymphocytes when stimulated with mitogens or antigens, the proliferative response of the PGE2(+) subset was poor. Moreover, PGE2(+) T lymphocytes did exert a strong suppressor activity on mitogen- or allogeneic cell-induced lymphocyte proliferation as well as on pokeweed mitogen-driven B cell maturation into Ig-containing cells. PGE2(-) T lymphocytes were shown not to exert a significant suppressor activity in these assays. The PGE2(+) subset-mediated suppression was not secondary to a carry-over of PGE2 released from the beads, because its suppressor activity was not altered by the addition of an anti-PGE2 serum. Moreover, PGE2(-) T lymphocytes were not sensitive to the inhibitory activity on cell proliferation of PGE2. These results indicate that a given functional subset of peripheral blood T lymphocytes binds PGE2, and that at least some of them are activated into suppressor T cells. The relationship between the PGE2-activatable T suppressor subset and other functionally defined suppressor T cells remains to be clarified; it is suggested, however, that PGE2 can act as an immunoregulator through the activation of identifiable suppressor T cells.

Antibodies, Monoclonal↗
PubMed1985

[Severe combined immune deficiency with hypereosinophilia. Immunologic study of 5 cases].

We herein report five new cases of severe combined immunodeficiency with hypereosinophilia, the so-called familial reticuloendotheliosis first described by Omenn. It is characterized by erythroderma, polyadenopathy, hepatosplenomegaly, severe and repeated infections, protracted diarrhoea with failure to thrive. There is marked eosinophilia as well as a profound immunodeficiency. The immunologic abnormalities consist of an increase in T cell number, a B cell lymphopenia and a complete lack of humoral and cellular immune responses to antigens. A deficiency of lymphocytes 5'-nucleotidase has been inconstantly found. Histologic findings are characteristic, consisting of severe T and B lymphocyte depletion in lymphoid organs with infiltration by histiocytes and, to a lesser extent, eosinophils. The outcome was uniformly fatal within the first year of life. Treatment by a combination of parenteral nutrition, steroids and epipodophyllotoxin was effective in obtaining the complete remission of clinical manifestations due to the histiocytic and eosinophilic infiltration in two patients. However, the treatment failed to correct the immunologic defect. These results indicate that the histiocytic infiltration is possibly not responsible for the immunologic detect observed in this condition.

5'-Nucleotidase↗
PubMed1985

[Prenatal diagnosis of severe hereditary immunologic deficiencies].

The recent progress in antenatal diagnosis methods led us to develop the antenatal diagnosis of several forms of hereditary and severe immune deficiencies (ID): severe combined ID (13 cases), combined ID associated with a defective expression of HLA (2 cases), X-linked agammaglobulinemia (4 cases), chronic granulomatous disease (1 case). Antenatal diagnosis was performed by studying by micromethods lymphocyte markers and functions in fetal venous blood samples obtained under foetoscopy (20 cases) or echography (1 case). Cytological studies were coupled with microscopical examination of the skin and the hair of a foetus at risk for a Chediak-Higashi disease. These methods allowed the continuation of the pregnancy in 16 cases. Thirteen neonates were normal and two pregnancies go on. In one case, the diagnosis of the integrity of the immune system led to the birth of a child suffering from a severe combined ID not yet described. This child was cured with a HLA semi-identical bone-marrow transplantation. An abortion was proposed for two fetuses affected with severe combined ID which was confirmed by histological examination. Two accidental abortions occurred, one of them probably as a consequence of the fetoscopy.

Female↗
PubMed1985

Enhanced plasminogen-activator production by leukocytes in the human and murine Chediak-Higashi syndrome.

We have studied the coagulation status of eight patients with the Chediak-Higashi syndrome (CHS), both in the chronic and the accelerated phase of the disease. It has been shown that during the accelerated phase there are coagulation abnormalities. These abnormalities include a peripheral thrombocytopenia, minor alterations of liver clotting factors, and mainly a profound hypofibrinogenemia and hypoplasminogenemia, which cause life-threatening bleedings. These disorders are of complex origin, but a fibrinolytic process, possibly primary, appears to play a significant role, since the present evidence for intravascular coagulation is not definitive. The accelerated phase of the CHS is characterized by a visceral infiltration by macrophages and lymphocytes. Therefore, we have investigated the possible role of the macrophages in the fibrinolytic process. We have found an excessive plasminogen activator (PA) production by CHS mononuclear cells in the accelerated phase and to a lesser extent in the chronic phase, except in one patient in whom no anomaly was found. Single-cell studies revealed an increased number of PA-producing cells among the monocyte-macrophage lineage rather than a higher level of production per cell. Polymorphonuclear cells (PMN) from patients with CHS were also shown to contain more PA. Slight but significant abnormalities in PA production were observed in obligatory heterozygotes (five out of nine), indicating the inherited nature of the excessive PA production. Finally, an enhanced PA production was similarly demonstrated using beige mice macrophages. The exacerbated production of PA by macrophages in the accelerated phase of the CHS can account to some extent for the coagulation abnormalities that have been observed.

Acute Disease↗
PubMed1984

[Treatment of the Wiskott-Aldrich syndrome by a graft of allogeneic bone marrow].

We herein describe the first French case of successful bone marrow transplantation (BMT) in a patient with the Wiskott-Aldrich syndrome. Although the patient required hospitalization for a total of one year during his first 4 years of life for bleeding, eczema, protracted diarrhea and multiple infections, the bone marrow transplantation has permitted a complete and stable correction of the thrombocytopenia, the eczema and the immunodeficiency. The patient was prepared by a total body irradiation (850 rads) with a partial lung shielding and anti-lymphocyte globulins. The BMT was immediately followed by a severe but transient herpetic infection and acute graft versus host reaction (grade II) which resolved after steroid therapy. The thrombocytopenia disappeared 3 months after the BMT. The infections and the eczema did not reappear. Immune functions are entirely normal and all blood cells have been shown to be of donor origin (the sister of the recipient). The boy is growing normally and is doing well 3 1/2 years thereafter. He only suffered from bilateral cataracts secondary to the irradiation requiring lens extraction. One can now expect a success rate of 75% in bone marrow transplantation in patients with Wiskott-Aldrich syndrome as evaluated from a world review. In contrast, symptomatic treatment of the disease leads to a mean survival of 7 years, survival rarely exceeding 18 years.

Bone Marrow Transplantation↗
PubMed1983

[Activation by injectable gamma globulins of the suppressive functions of the humoral response tested in vitro].

In subjects with normal immune system injectable gammaglobulins produce unexpected effects: B cells become unable to mature into plasmocytes in vitro when cultured in the presence of pokeweed mitogen. This inhibitory effect seems to be associated with binding of the denatured gammaglobulins to B cell membrane receptors for the IgG Fc fragment (Fc gamma). In addition, injectable gammaglobulins activate a radiosensitive suppressor T cell population without Fc receptors for IgG. Activation of the suppressive function inhibiting of B cells into plasmocytes results from excessive secretion of prostaglandin E2 (PGE 2) by monocytes. We have previously demonstrated that PGE 2 in excess activates certain suppressor T cells. The secretion of PGE 2 by monocytes is thought to be associated with the binding of denatured IgG's to membrane receptors for the corresponding Fc. Activation of suppressor T cells was reproduced in vitro by incubating total T cells or T cells without Fc gamma receptors in the presence of either complete gammaglobulins or of the aggregates they contain. In contrast, preparations deprived of aggregates and F (ab)'2 fragments isolated from gammaglobulins do not produce any detectable activation of suppressor T cells. The results obtained in vitro may not necessarily correspond to the effects of injectable gammaglobulins on humoral response in vivo. We should point out, however, that a fall in plasma IgE levels may be observed in some subjects and that in exceptional cases of IgG and IgA hypergammaglobulinaemia a fall in IgG and IgA has been recorded after gammaglobulin injections.

Antibody Formation↗
PubMed1983

Bone-marrow transplantation for inborn error of phagocytic cells associated with defective adherence, chemotaxis, and oxidative response during opsonised particle phagocytosis.

Two girls had delayed umbilical cord detachment, recurrent bacterial infection, inability to form pus, and marked leucocytosis. Their phagocytes were defective in tests of adherence, random migration, chemotaxis, and oxidative burst. NK activity was virtually absent. This rare disorder, due to an inherited absence of a 180 kilodalton membrane glycoprotein on polymorphonuclear cells, is usually lethal within 2 years. Allogeneic HLA-matched bone-marrow transplantation done at ages 4 months in one patient and 2 years in the other after intensive conditioning was successful and resulted in nearly complete correction of phagocytic cell function and NK activity within two months. One patient died 9 months after transplantation from severe chronic graft-versus-host disease with obstructive bronchopneumopathy. The other is doing well 1 year after transplantation and showing stable chimerism and normal phagocytic function.

Bone Marrow Transplantation↗
PubMed1983

Specific in vitro antimannan-rich antigen of Candida albicans antibody production by sensitized human blood lymphocytes.

We have developed a new antigenic system for the induction of specific in vitro antibody response in man. The antigen used was purified from the cell wall of Candida albicans strain A and contained greater than 96% polysaccharide mannan. Peripheral blood mononuclear cells from Candida-sensitized donors produced specific antimannan antibodies during a 7-d culture in the presence of mannan absorbed with methylated bovine serum albumin. Two methods were used to detect antimannan antibody responses. Antimannan antibody-producing cells were identified by radioautography with tritiated mannan. Antibody concentration in culture supernatants was measured by an enzyme-linked immunosorbent assay. In both methods, specific IgM and IgG (but not IgA) antibodies were detected. The antibody production to mannan was specific, since an antigenically unrelated polysaccharide (pneumococcal antigen S III) did not bind to methylated bovine serum albumin-mannan-induced blast cells and did not induce antimannan antibody-containing cells. Furthermore, a pulse with an excess of unlabeled mannan abolished [3H]mannan binding, whereas an excess of unlabeled S III did not. Similarly, no antimannan antibody was obtained in influenza virus-stimulated cultures and mannan-stimulated cultures were not inducing antiinfluenza antibodies. The antimannan antibody production was shown to be a T cell-dependent phenomenon. The T helper effect appeared to be radiosensitive. It was under a genetic restriction as it occurred only in autologous or semi-identical but not in allogeneic situations. This system is relatively simple, reproducible, and well suited for the study of specific secondary in vitro antibody responses to polysaccharide antigens in humans.

Antibodies, Fungal↗
PubMed1983

Enhancement by interferon of membrane HLA antigens in patients with combined immunodeficiency with defective HLA expression.

Since interferon is known to enhance HLA A-B expression on lymphocytes from normal donors, we have tested the hypothesis that interferon could reverse the defective membrane expression of HLA antigens observed in some patients with combined immunodeficiency. Leucocytes from four patients with this syndrome, after overnight incubation with preparations of interferon, showed a clear enhancement in the percentage of cells bearing HLA A-B-C and beta 2 microglobulin (but not HLA-DR) antigens as detected by membrane immunofluorescence. Functional HLA-A and B antigens also appeared on patients' T cell blasts treated with interferon, as shown by the ability of these blasts to be destroyed by specific cytotoxic T lymphocytes. Both alpha and beta human interferons were effective. These effects were shown to be mediated by interferon (but not contaminants in our preparations) by the use of specific antiserum to interferon. It is likely that interferon acts on HLA synthesis, since in vitro addition of drugs known to inhibit nucleic acid or protein synthesis completely abolished the enhancing effect of interferon on membrane HLA expression. Interferons can therefore modulate leucocyte HLA expression and synthesis in patients with defective expression of these antigens, a finding which suggests that interferon treatment might be beneficial in this condition.

Antigens, Surface↗