Search PubMed⌕ Search

Biomedical subjects

I Durand

Publications and source records attributed to I Durand.

At least 37 records · Page 2Linked to original sources
PubMed1997

Human dendritic cells skew isotype switching of CD40-activated naive B cells towards IgA1 and IgA2.

Within T cell-rich areas of secondary lymphoid organs, interdigitating dendritic cells recruit antigen-specific T cells that then induce B cells to secrete Igs. This study investigates the possible role(s) of dendritic cells in the regulation of human B cell responses. In the absence of exogenous cytokines, in vitro generated dendritic cells (referred to as Dendritic Langerhans cells, D-Lc) induced surface IgA expression on approximately 10% of CD40-activated naive sIgD+ B cells. In the presence of IL-10 and TGF-beta, a combination of cytokines previously identified for its capacity to induce IgA switch, D-Lc strongly potentiated the induction of sIgA on CD40-activated naive B cells from 5% to 40-50%. D-Lc alone did not induce the secretion of IgA by CD40-activated naive B cells, which required further addition of IL-10. Furthermore, D-Lc skewed towards the IgA isotype at the expense of IgG, the Ig production of CD40-activated naive B cells cultured in the presence of IL-10 and TGF-beta. Importantly, under these culture conditions, both IgA1 and IgA2 were detected. In the presence of IL-10, secretion of IgA2 by CD40-activated naive B cells could be detected only in response to D-Lc and was further enhanced by TGF-beta. Collectively, these results suggest that in addition to activating T cells in the extrafollicular areas of secondary lymphoid organs, human D-Lc also directly modulate T cell-dependent B cell growth and differentiation, by inducing the IgA isotype switch.

Antigens, CD34↗
PubMed1997

The enigmatic plasmacytoid T cells develop into dendritic cells with interleukin (IL)-3 and CD40-ligand.

A subset of CD4+CD11c-CD3- blood cells was recently shown to develop into dendritic cells when cultured with monocyte conditioned medium. Here, we demonstrate that CD4+ CD11c-CD3- cells, isolated from tonsils, correspond to the so-called plasmacytoid T cells, an obscure cell type that has long been observed by pathologists within secondary lymphoid tissues. They express CD45RA, but not markers specific for known lymphoid- or myeloid-derived cell types. They undergo rapid apoptosis in culture, unless rescued by IL-3. Further addition of CD40-ligand results in their differentiation into dendritic cells that express low levels of myeloid antigens CD13 and CD33.

Antigens, CD↗
PubMed1997

Isoenzyme diversity in Pneumocystis carinii from rats, mice, and rabbits.

Pneumocystis carinii is an opportunistic pathogen that causes pneumonia in immunocompromised patients. To investigate the genetic diversity of P. carinii populations, multilocus enzyme electrophoresis was used to analyze five enzyme systems (malate dehydrogenase, glucose phosphate isomerase, leucine aminopeptidase, malic enzyme, and 6-phosphogluconate dehydrogenase). Only five different multilocus associations (zymodemes) were recorded for the 70 isolates studied. While only one multilocus combination was found in mice and rabbits, three different multilocus associations were recorded in rats. Population genetic tests and phylogenetic analysis strongly suggest that P. carinii genotypes are host-specific, in agreement with molecular study results, and that no genetic exchange occurs between genotypes from different host species. This hypothesis could be verified only by the evolutionary genetic approach, which relies here on multilocus analysis.

Animals↗
PubMed1997

[Disproportion in diameter of the cardiac chambers and great arteries in the fetus. Contribution to the prenatal diagnosis of coarctation of the aorta].

The aim of this study was to identify simple echocardiographic criteria suggesting the presence of coarctation of the aorta in the antenatal period. This was a retrospective cooperative study of 43 cases of foetal echocardiography referred to a paediatric cardiologist for abnormal dimensions of the left cardiac chambers and vessels compared with 102 control foetus. Eighteen (41.8%) had abnormalities of the aortic arch at birth. Thirteen of the 18 (72%) neonates had aortic arch abnormalities when disequilibrium with a small left heart was observed before 25 weeks amenorrhea. The ratio between the right and left ventricular dimensions was abnormally high in foetus with functional disequilibrium similar to the foetus with coarctation: the difference between the two groups was not significant. The ratio of pulmonary artery to aortic dimension was higher in the foetus with coarctation of the aorta than with functional disequilibrium. The difference was significant: p < 0.0001. The diameter of the aortic arch in foetus with a future coarctation was much smaller than the mean of the controls, except in 4 cases. The majority of the foetus without left-sided obstacles at birth had normal aortic arches. An early disequilibrium, a high pulmonary artery/aortic ratio and the small size of the aortic ischmus were the main elements suggestive of abnormalities of the aortic arch, especially in the early prenatal period.

Aorta, Thoracic↗
PubMed1996

Dendritic cells capable of stimulating T cells in germinal centres.

The B cells within the germinal centres of lymphoid organs undergo affinity maturation of their antigen receptors, a critical event for antibody memory. Follicular dendritic cells within the germinal centres retain immune complexes that select the developing B cells for which they have a higher affinity. We have now identified a subset of CD4+ CD11c+ CD3- dendritic cells in the germinal centres. These are strong antigen-presenting cells for T cells, but do not co-stimulate CD40-activated B cells. These dendritic cells probably stimulate germinal centre T cells and aid the complicated processes that are required for the generation of memory B cells.

Antigen Presentation↗
PubMed1996

Demonstration of functional CD40 in B-lineage acute lymphoblastic leukemia cells in response to T-cell CD40 ligand.

Because activated T cells were previously shown to induce proliferation of human normal B-cell precursors (BCP) via the CD40 pathway, we investigated the effects of T cells on leukemic blasts isolated from patients with B-lineage acute lymphoblastic leukemia (BCP-ALL). An anti-CD3 activated human CD4+ T-cell clone was found to induce significant call proliferation in four of nine BCP-ALL samples analyzed. In one of these cases, the T-cell effect was clearly dependent on interaction between CD40 and its ligand. Accordingly, a more thorough analysis was performed on this particular leukemia (case 461, adult early pre-B-ALL, mBCR+, Philadelphia+, i(9q)+). Thus, autologous CD4+ T cells isolated from the patient were also able to induce CD40-dependent proliferation of the leukemic blasts. Analysis of the phenotype after coculture showed that, among the CD19+ cells, a proportion gradually lost expression of CD10 and CD34, whereas some cells acquired CD23. In addition, and in contrast with normal BCP, activated T cells promoted maturation of a subset of the case 461 leukemic cells into surface IgM+ cells. The leukemic origin of the cycling and the maturing cells was assessed by the presence of i(9q), a chromosomal abnormality associated with this leukemia and evidenced by fluorescence in situ hybridization. Taken together, these results show that leukemic BCP can be activated via CD40 but that not all cases display detectable stimulation in response to T cells despite their expression of CD40. In addition, the present data suggest that CD4+ T cells could potentially play a role in the physiology of BCP-ALL.

Adult↗
PubMed1996

Inability to produce IL-6 is a functional feature of human germinal center B lymphocytes.

In response to Ag encounter, B lymphocytes undergo a complex maturation process yielding phenotypically distinct subpopulations that are located in highly organized compartments of secondary lymphoid organs. This study describes the patterns of cytokine secretion of naive, memory, and germinal center (GC) human tonsillar B lymphocytes, activated either through CD40 or B cell receptor or with Staphylococcus aureus Cowan I particles. The three B cell subpopulations produced comparable levels of IL-10 and TNF-alpha, regardless of the stimulation pathway. Interestingly, activated GC B lymphocytes fail to express IL-6, as determined both at mRNA and at protein levels, whereas both naive and memory B cells can be induced to secrete IL-6. Likewise, naive B lymphocytes undergoing dual ligation of CD40 and B cell receptor fail to express IL-6, since they acquire a GC-like phenotype. IL-6 receptors are up-regulated on both ex vivo-purified GC B lymphocytes and in vitro generated GC-like B cells, following CD40 activation. Consistent with this, addition of exogenous IL-6 sustains growth of CD40-stimulated GC B lymphocytes. Taken together, these results demonstrate that loss of IL-6 secretion is a functional characteristic of human GC B lymphocytes. The swap from an autocrine to a paracrine IL-6 response may permit a better control of B cell growth and differentiation during the germinal center reaction.

Antilymphocyte Serum↗
PubMed1996

Negative selection of human germinal center B cells by prolonged BCR cross-linking.

The antigen receptors on T and B lymphocytes can transduce both agonist and antagonist signals leading either to activation/survival or anergy/death. The outcome of B lymphocyte antigen receptor (BCR) triggering depends upon multiple parameters which include (a) antigen concentration and valency, (b) duration of BCR occupancy, (c) receptor affinity, and (d) B cell differentiation stages. Herein, using anti-immunoglobulin kappa and lambda light chain antibodies, we analyzed the response of human naive, germinal center (GC) or memory B cells to BCR cross-linking regardless of heavy chain Ig isotype or intrinsic BCR specificity. We show that after CD40-activation, anti-BCR (kappa + gamma) can elicit an intracellular calcium flux on both GC and non-GC cells. However, prolonged BCR cross-linking induces death of CD40-activated GC B cells but enhances proliferation of naive or memory cells. Anti-kappa antibody only kills kappa + GC B cells without affecting surrounding gamma + GC B cells, thus demonstrating that BCR-mediated killing of GC B lymphocytes is a direct effect that does not involve a paracrine mechanism. BCR-mediated killing of CD40-activated GC B cells could be partially antagonized by the addition of IL-4. Moreover, in the presence of IL-4, prestimulation through CD40 could prevent subsequent anti-Ig-mediated cell death, suggesting a specific role of this combination in selection of GC B cells. This report provides evidence that in human, susceptibility to BCR killing is regulated along peripheral B cell differentiation pathway.

Antibodies, Anti-Idiotypic↗
PubMed1996

Interleukin-3 cooperates with tumor necrosis factor alpha for the development of human dendritic/Langerhans cells from cord blood CD34+ hematopoietic progenitor cells.

We have previously shown that tumor necrosis factor (TNF)alpha strongly potentiates the granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin (IL)-3-dependent proliferation of CD34+ hematopoietic progenitor cells (HPC) through the recruitment of early progenitors with high proliferative potential. Furthermore, the combination of GM-CSF and TNFalpha allows the generation of large numbers of dendritic/Langerhans cells (D-Lc). Herein, we analyzed whether IL-3, when combined to TNFalpha would, as does GM-CSF, allow the generation of CD1a+ D-Lc. Accordingly, cultures of cord blood CD34+ HPC with IL-3 + TNFalpha yielded 20% to 60% CD14+ cells and 11% to 17% CD1a+ cells, while IL-3 alone did not generate significant numbers of CD1a+ cells. Although the percentage of CD1a+ cells detected in IL3 + TNFalpha was lower than that observed in GM-CSF + TNFalpha (42% to 78%), the strong growth induced by IL-3 + TNFalpha generated as many CD1a+ cells as did GM-CSF + TNFalpha. The CD14+ and CD1a+ cells generated with IL-3 + TNFalpha are similar to CD14+ and CD1a+ cells generated in GM-CSF alone and GM-CSF + TNFalpha, respectively. CD1a+ cells differed from CD14+ cells by (1) dendritic morphology, (2) higher expression of CD1a, CD1c, CD4, CD40, adhesion molecules (CD11c, CD54, CD58), major histocompatibility complex (MHC) class II molecules and CD28 ligands (CD80 and CD86), (3) lack of Fc receptor FcgammaRI (CD64) and complement receptor CR1 (CD35) expression, and (4) stronger induction of allogeneic T-cell proliferation. Thus, in combination with TNFalpha, IL-3 is as potent as GM-CSF for the generation of CD1a+ D-Lc from cord blood CD34+ HPC. The dendritic cell inducing ability of IL-3 may explain why mice with inactivated GM-CSF gene display dendritic cells.

Adult↗
PubMed1996

Nerve growth factor-induced accumulation of PC12 cells expressing cyclin D1: evidence for a G1 phase block.

The anti-proliferative effect of nerve growth factor (NGF) on the rat pheochromocytoma cell line PC12 has been previously shown to be accompanied by the accumulation of cells in either the G1 phase with a 2c DNA content, or with a 4c DNA content characteristic for G2/M, as evidenced by flow cytometric analysis of DNA distribution using propidium iodide. Herein, these apparently conflicting results are clarified. The present studies indicate that a simple DNA distribution profile obtained by this technique can confound interpretation of the biological effects of NGF on cell-cycle distribution due to the presence of tetraploid cells. Using cyclin D1 and incorporation of bromodeoxyuridine as markers of respectively, G1 and S phase, we show that PC12 cultures can have a considerable amount of tetraploid cells which, when in the G1 phase, have a 4c DNA content and express cyclin D1. During exposure to NGF, this population increases, reflecting the accumulation of cells in the G1 phase of the cell cycle. The data presented, support the possibility that events affecting the expression or action of G1 regulatory proteins may be involved in the molecular mechanism of the anti-mitogenic effect of NGF.

Adrenal Gland Neoplasms↗
PubMed1996

Bcl-2+ tonsillar plasma cells are rescued from apoptosis by bone marrow fibroblasts.

Plasma cells represent the final stage of B lymphocyte differentiation. Most plasma cells in secondary lymphoid tissues live for a few days, whereas those in the lamina propria of mucosa and in bone marrow live for several weeks. To investigate the regulation of human plasma cell survival, plasma cells were isolated from tonsils according to high CD38 and low CD20 expression. Tonsillar plasma cells express CD9, CD19, CD24, CD37, CD40, CD74, and HLA-DR, but not CD10, HLA-DQ, CD28, CD56, and Fas/CD95. Although plasma cells express intracytoplasmic Bcl-2, they undergo swift apoptosis in vitro and do not respond to CD40 triggering. Bone marrow fibroblasts and rheumatoid synoviocytes, however, prevented plasma cells from undergoing apoptosis in a contact-dependent fashion. These data indicate that fibroblasts may form a microenvironment favorable for plasma cell survival under normal and pathological conditions.

Antigens, CD↗
PubMed1996

The functional CD40 antigen of fibroblasts may contribute to the proliferation of rheumatoid synovium.

This paper demonstrates that CD40 is expressed on rheumatoid synovial pannus and primary fibroblast cell lines established from rheumatoid and osteoarthritic synovium as well as normal skin. Among various tested cytokines, interferon-gamma (IFN-gamma) and to a lower extent, tumour necrosis factor-alpha (TNF-alpha) were found to upregulate CD40 expression on fibroblasts. Synovial and skin fibroblasts cultured over CD40 Ligand transfected L cells (L-CD40 L) demonstrate a CD40 specific increase of DNA synthesis as measured by tritiated thymidine incorporation. Cell-cycle analysis and enumeration of viable cells further show that CD40 induced fibroblast proliferation. Costimulation with L-CD40 L and IFN-gamma resulted in maximal proliferation. Engagement of fibroblasts CD40 increased the IL-1-induced production of granulocyte macrophage-colony stimulating factor and macrophage inflammatory protein-1 alpha MIP-1 alpha. CD40 L activated fibroblasts showed decreased levels of CD40, but only marginal alterations of other cell-surface antigens. Taken together, the present results indicate that fibroblasts express functional CD40 and suggest a possible role of CD40 L expressing cells, such as activated T cells and mast cells, in the development of synovium hyperplasia.

Animals↗
PubMed1995

Isolation and characterization of an avian A1 adenosine receptor gene and a related cDNA clone.

We have isolated the gene for a chick A1 adenosine receptor along with a cDNA that codes for the same adenosine receptor. The cDNA clone was isolated from both adipose tissue and heart cDNA libraries and encodes a 324-amino acid protein with 80% identity with mammalian A1 adenosine receptors. Transient expression of the cDNA in human embryonic kidney (HEK) 293 cells shows that it encodes a protein that binds [3H]CCPA (2-chloro-N6-[cyclopentyl-2,3,4,5-3H]cyclopentyladenosine, a specific agonist radioligand, with a KD of 5.6 +/- 2.4 nM. Cyclic AMP measurements in HEK 293 cells co-transfected with the chick cDNA and a cDNA for a luteinizing hormone/choriogonadotropin receptor shows that A1 adenosine receptor agonists antagonize the cyclic AMP-elevating effect of bovine luteinizing hormone. Two partial genomic clones were isolated. The first contains 5'-untranslated sequence including a putative promoter region which does not contain a TATA box, an intron and the first third of the coding sequence of the A1 adenosine receptor cDNA. The coding sequence of this partial genomic clone terminates at a second intron. The second partial genomic clone contains the rest of the coding sequence and the 3'-untranslated elements in a single exon. Thus the chick A1 adenosine receptor gene contains one intron in the 5'-untranslated region and a minimum of one intron in the coding sequence.

Adenosine↗
PubMed1995

High frequency of IL-10-secreting CD4+ graft-infiltrating T lymphocytes in promptly rejected kidney allografts.

IFN-gamma and IL-10 secretion by sorted T cell subsets of irreversibly rejected kidney graft-infiltrating cells (GIC) and normal PBMC was studied by ELISPOT. The low spontaneous frequency of IFN-gamma-producing cells (IFN-gamma-PC) was strongly increased by anti-CD3 activation within unsorted, CD3+CD4+, and CD3+CD4- subsets of GIC and PBMC. In contrast with PBMC, IL-10-PC from GIC were at higher frequency within CD4+ cells than among CD4- ones (P < 0.03). Four kidneys removed after 3.7 +/- 0.8 months showed acute vascular rejection, high frequency of activated CD4+ IL-10-PC (118 +/- 68 per 10(4) cells), and high percentage of anti-class II antibody reactivity (87.6 +/- 6.3%). In contrast, four patients with kidneys removed later (53.7 +/- 1.6 months, P = 0.02) displayed chronic rejection with superimposed acute cellular rejection, low frequency of CD4+ IL-10-PC (7.0 +/- 3.0 per 10(4) cells, P = 0.02), and low percentage of anti-class II antibody reactivity (12.9 +/- 6.1%, P = 0.02). Thus, accelerated vascular rejection appears to be associated with preferential production of IL-10 by activated CD4+ GIC, which may act by shifting the effector arms of alloreaction toward humoral responses.

Acute Disease↗
PubMed1995

Anti-CD40 plus interleukin-4-activated human naive B cell lines express unmutated immunoglobulin genes with intraclonal heavy chain isotype variability.

Combination of anti-CD40 antibody and interleukin-4 (IL-4) induces B cell clonal expansion reminiscent of the T-dependent proliferation following antigenic challenge in vivo. We have analyzed the usage of CH genes and the presence or absence of somatic mutations within the progeny of a single human naive B cell activated with anti-CD40 + IL-4. To address this issue, single-cell cultures of naive (sIgD+) tonsillar B lymphocytes expressing the VH1-restricted G8 idiotype were set up. After culture and RNA extraction, VH1+ Ig mRNA were reverse-transcribed, amplified by polymerase chain reaction and sequenced. A single sIgD+ B cell could generate clones expressing mu, gamma 1, gamma 3, or epsilon, illustrating that the progeny of a single cell can express different isotypes in response to the same stimulus in vitro. The rate of somatic mutations affecting the immunoglobulin variable heavy chain gene was indistinguishable from the background of errors introduced by Taq polymerase.

Antibodies, Anti-Idiotypic↗
PubMed1995

[Hypoplasia of abdominal aorta, rare cause of hypertension in childhood].

BACKGROUND: The majority of children with secondary hypertension have a renal abnormality or renovascular lesions. Coarctation of the aorta is also a classical cause, rarely located to the abdominal aorta. CASE REPORTS: Two girls, 11 and 12 years-old, were suspected of having recent sustained hypertension. Pulsed-wave doppler ultrasonography and angiography showed abdominal aortic hypoplasia associated with renal artery stenosis, unilateral in one patient and bilateral in the other. Both patients became normotensive 10 and 18 months, respectively, after corrective vascular surgery. CONCLUSION: Examination of the abdominal part of the aorta is mandatory in all patients with hypertension.

Aorta, Abdominal↗