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Biomedical subjects

B Dupont

Publications and source records attributed to B Dupont.

At least 253 records · Page 14Linked to original sources
PubMed1988

Allogeneic T cell activation triggering by MHC class I antigens.

The role of MHC-encoded class I molecules in allogeneic activation and proliferation of human T lymphocytes was investigated. The study was performed by using primary mixed culture of lymphocytes from MHC recombinant siblings identical for MHC class II Ag (DR, DP, DQ) and displaying MHC class I disparity. The results indicate that such allogeneic combination is sufficient to trigger early activation steps within responder T cells without promoting a significant proliferation. After MHC class I allosensitization, a significant proportion of cells entered the cell cycle (G0----G1). The stimulatory potential of MHC class I Ag was further stressed by the specific induction on responder cells of IL-2R (22% T cell activation Ag positive). Under the same experimental conditions, transferrin receptor expression and IL-2 activity were not detectable. This is consistent with the low T cell proliferation. Exogenous rIL-1 did not improve IL-2 production and the subsequent T cell proliferation indicating that these two events were not associated with a defective accessory cell function involving IL-1 release. MHC class I disparity can also prime precursor CTL to differentiate into IL-2-dependent functional MHC restricted cytotoxic T cells. Conversely IFN-gamma had no effect. Addition to the culture of W6/32, a mAb specifically directed against a monomorphic determinant on human class I HLA-A, -B, and -C Ag was able to block all these activation events. These data clearly indicate a role of HLA class I Ag involvement in the early events triggering allogeneic T cell activation.

Antibodies, Monoclonal↗
PubMed1988

Treatment of steroid-resistant acute graft-vs-host disease by in vivo administration of an anti-T-cell ricin A chain immunotoxin.

The A chain of the toxin ricin has been conjugated by a disulfide bond to a murine monoclonal antibody that recognizes the CD5 (T,p67) antigen present on 95% of peripheral blood T lymphocytes. This immunotoxin was used to treat a patient with severe grade III-IV, steroid-resistant, acute graft-vs-host disease (GvHD) after an allogeneic, human leukocyte antigen-identical bone marrow transplant for acute myelogenous leukemia. Immunotoxin therapy produced a complete clinical response in the skin and gastrointestinal tract. The patient tolerated a 14-day course without symptoms or signs of toxic effects. After two days of therapy, circulating T cells could not be demonstrated by indirect immunofluorescence. After therapy, acute GvHD did not recur. However, seven months after therapy the patient demonstrated mild signs of chronic GvHD that were easily controlled with low-dose immunosuppressive therapy. These findings indicate that an anti-T-cell ricin A chain immunotoxin can be given safely for treatment of acute GvHD and may be an effective therapy for this significant posttransplant complication.

Acute Disease↗
PubMed1988

Isolation and nucleotide sequence of a cDNA clone encoding a novel HLA class I gene.

A cDNA clone, designated JTW15, has been isolated and found to encode a novel, divergent class I HLA gene transcript. The clone was identified by its ability to hybridize with a pan-HLA class I nucleotide probe while failing to bind probes specific for the 3' untranslated exons of the HLA-A, -B, and -C genes. JTW15, 1665 nucleotides in length, represents a full length copy of an approximately 1.7-kb mRNA detected in Northern blot analyses. Comparison of the derived amino acid sequence with those of other HLA class I proteins showed JTW15 to be the most divergent HLA class I gene identified so far, the level of sequence homology being lowest for the alpha 1 and alpha 2 domains. The JTW15 gene transcript was found in a broad variety of cell types and was inducible in cells treated with IFN-gamma. JTW15 is the first isolated full length cDNA clone defining a non-HLA-ABC class I gene.

Amino Acid Sequence↗
PubMed1988

Differential in vitro activation of CD8-CD4+ and CD4-CD8+ T lymphocytes by combinations of anti-CD2 and anti-CD3 antibodies.

Purified peripheral blood T lymphocytes and the CD8-CD4+ and CD4-CD8+ T cell subsets, exhaustively depleted of APC have been studied for their capacity to respond to mAb directed against the CD3-Ti Ag-specific TCR complex and against the CD2 SRBCR. It is demonstrated that high affinity IL-2R can be readily induced by either anti-CD3 and/or anti-CD2 stimulation. However, IL-2 production can be observed only in the CD4+CD8- T cell subset. These results clearly contrast data obtained with purified CD4-CD8+ T cells, which are able to proliferate when the CD3-Ti complex is activated in the presence of APC. The data presented in the present study demonstrate that a simplified model for T cell activation and clonal expansion of the two major T cell subsets involve only the CD3-Ti complex and the CD2 Ag. Under conditions where the activation signals for the T cells are restricted only to the activation of CD3-Ti and CD2, the CD4+CD8- T cells respond with IL-2 production and expression of high affinity IL-2R, whereas the CD4-CD8+ T cell subset depends on exogenous IL-2 provided by the CD4+CD8- cells. These data do not, however, exclude an involvement of other cell-surface signals for regulation and control of T cell activation and T cell effector functions.

Antibodies, Monoclonal↗
PubMed1988

Comparison of the structure of HLA-Bw47 to HLA-B13 and its relationship to 21-hydroxylase deficiency.

Adrenal 21-hydroxylase deficiency is strongly associated with HLA-Bw47. This rare HLA allele and the HLA-B13 allele are both found in positive genetic linkage disequilibrium with HLA-A3, -Cw6, -DR7 and also display serological cross-reactivity. To investigate the relationship between these two alleles at the structural level, the nucleotide sequences of the HLA-B13 and HLA-Bw47 genes have been determined. They differ by 28 nucleotides, resulting in 14 amino acid substitutions: 5 in the alpha 1 domain, 8 in the alpha 2 domain, and 1 in the transmembrane region. Comparison of HLA-Bw47 nucleotide sequence with other HLA-B sequences shows a segment of 228 bp identical with B44 in the alpha 1 domain and a segment of 218 bp identical with B27 in the alpha 2 domain, but only a 91 bp segment of identity with B13 in the alpha 1 domain. The complex pattern of substitutions and their degree of divergence indicate that HLA-B13 and HLA-Bw47 alleles are not related by a simple mutational event.

Adrenal Hyperplasia, Congenital↗
PubMed1988

Tolerance of engrafted donor T cells following bone marrow transplantation for severe combined immunodeficiency.

Patients transplanted for the treatment of severe combined immunodeficiency (SCID) frequently develop a unique state of split lymphoid chimerism. Such patients have T cells of donor origin, and non-T cells which are predominantly or exclusively of host origin. We have studied the reactivity of engrafted donor T cells to host and/or donor antigens in 12 patients transplanted for SCID, focusing on the characteristics of the tolerance to host and/or donor MHC antigens observed in nine of these patients who were recipients of T-cell-depleted, haploidentical parental bone marrow. In both proliferative and cytolytic assays, engrafted, donor-derived T cells were shown to be selectively nonreactive to histoincompatible host cells. This tolerance could not be ascribed to cells with suppressive activity in the engrafted T-cell population. T cells from a subset of patients, however, exhibited proliferative but not cytolytic reactivity to donor peripheral blood mononuclear cells. The responding cells were shown to be donor-derived CD3+ cells and were predominantly reactive to B-cell fractions from the donor. Two patients who received transplants from each parent in sequence engrafted T cells from one parent and had non-T cells of host, paternal, and maternal origin. The engrafted T cells proliferated weakly to B cells from the other parent, but were tolerant in cytolytic assays. Donor anti-donor reactivity was seen only in haploidentical split chimeras who had not been treated with cytotoxic drugs prior to T-cell engraftment. This proliferative reactivity toward donor may be due to an absence of donor derived Ia+ antigen presenting cells resident in the thymus of SCID patients at the time when the T-cell repertoire is being shaped.

B-Lymphocytes↗
PubMed1988

Characterization of frequent deletions causing steroid 21-hydroxylase deficiency.

Steroid 21-hydroxylase deficiency is caused by mutations in the CYP21B gene. This gene and a highly homologous pseudogene, CYP21A, alternate with the C4A and C4B genes encoding the fourth component of complement. Classical deficiency alleles are frequently caused by deletions of CYP21B or by gene conversions that transfer deleterious mutations from the CYP21A pseudogene to CYP21B. Gene conversions involving restriction enzyme sites that distinguish CYP21A [e.g., 3.2-kilobase (kb) Taq I fragment] and CYP21B (3.7-kb Taq I fragment) might be confused with actual deletions of CYP21B. To determine the incidence of this type of gene conversion, 15 chromosomes (in 13 families) with absent 3.7-kb Taq I fragments were studied. When hybridized with a 21-hydroxylase probe, all of these chromosomes were associated with absent 2.9-kb Kpn I fragments, 14 of 15 were associated with absent 2.4-kb Bgl II/EcoRI fragments, and 13 of 15 were associated with absent 10-kb Bgl II/EcoRI and 12-kb EcoRI fragments. Thirteen of 15 chromsomes had absent 6.0- or 5.4-kb Taq I fragments when hybridized with a C4 probe. Thus, 2 of 15 chromosomes do not carry deletions and may represent gene conversions; 13 of 15 chromosomes studied have a deletion of approximately equal to 30 kb, leaving behind the C4A gene and a single CYP21A-like gene. Hybridization with specific oligonucleotide probes showed that in all 13 cases this remaining CYP21 gene carried an 8-base-pair deletion, typical of CYP21A, that prevents synthesis of a functional protein. Thus, gene conversions are rarely confused with deletions as a cause of 21-hydroxylase deficiency.

Adrenal Hyperplasia, Congenital↗
PubMed1988

Molecular cloning of an inducible serine esterase gene from human cytotoxic lymphocytes.

A cDNA clone encoding a human serine esterase gene was isolated from a library constructed from poly(A)+ RNA of allogeneically stimulated, interleukin 2-expanded peripheral blood mononuclear cells. The clone, designated HSE26.1, represents a full-length copy of a 0.9-kilobase mRNA present in human cytotoxic cells but absent from a wide variety of noncytotoxic cell lines. Clone HSE26.1 contains an 892-base-pair sequence, including a single 741-base-pair open reading frame encoding a putative 247-residue polypeptide. The first 20 amino acids of the polypeptide form a leader sequence. The mature protein is predicted to have an unglycosylated Mr of approximately equal to 26,000 and contains a single potential site for N-linked glycosylation. The nucleotide and predicted amino acid sequences of clone HSE26.1 are homologous with all murine and human serine esterases cloned thus far but are most similar to mouse granzyme B (70% nucleotide and 68% amino acid identity). HSE26.1 protein is expressed weakly in unstimulated peripheral blood mononuclear cells but is strongly induced within 6-hr incubation in medium containing phytohemagglutinin. The data suggest that the protein encoded by HSE26.1 plays a role in cell-mediated cytotoxicity.

Amino Acid Sequence↗
PubMed1988

Fluconazole in the management of oropharyngeal candidosis in a predominantly HIV antibody-positive group of patients.

Seventy-one patients with oropharyngeal candidosis received treatment with fluconazole given as a single 50 mg capsule once daily. Of these patients 61 were HIV-antibody positive. Candidosis had been present in nearly all patients for a least one month prior to fluconazole treatment. The duration of daily therapy was 5-20 days and in many cases this was followed by a period of maintenance treatment using 50 mg fluconazole every 48 h. In all 42 symptomatic patients, clinical resolution of the infection occurred within 7 days. Significantly, this included the disappearance of dysphagia in four patients with proven candidal oesophagitis. A marked reduction, or eradication of oral yeasts occurred concomitantly in virtually all patients. Fluconazole was well tolerated by all patients and there were no significant changes in haematological or hepatic parameters that could be attributed to the drug. The results suggest that fluconazole is an appropriate treatment for oropharyngeal candidosis and comparative studies with other agents should now be conducted.

Adult↗
PubMed1988

[Deep mycoses].

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Humans↗