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Biomedical subjects

D Charron

Publications and source records attributed to D Charron.

At least 217 records · Page 12Linked to original sources
PubMed1986

Structure, biosynthesis, and polymorphism of chicken MHC class II (B-L) antigens and associated molecules.

Chicken MHC class II (B-L) antigens were immunoprecipitated by the monoclonal antibody TaP1 from inbred chicken splenic leukocytes and a lymphoblastoid B cell line (RP9), and were studied by two dimensional gel electrophoresis. B-L antigens are composed of one alpha and one beta chain that are noncovalently bound at the cell surface. In all haplotypes studied, a single acidic 34,000 dalton non-polymorphic chain was observed, whereas two polymorphic chains could be distinguished, differing in both pH and m.w. The alpha-beta heterodimer is associated during its maturation in the cytoplasm with several basic invariant molecules with m.w. ranging from 30,000 to 42,000 daltons. Treatment of cells with tunicamycin and treatment of immunoprecipitated molecules with several glycosidases revealed a complex process of maturation for all of these molecules. The alpha and beta chains undergo a N-glycosylation of complex type, whereas the invariant molecules bear N-linked high mannose glycans, and perhaps also O-linked glycans in the RP9 lymphoblastoid line. Overall, the B-L antigens appear very similar to the HLA-DR and I-E antigens.

Animals↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

[A model and 3 examples for understanding HLA and diseases: cis and trans complementation of MHC class II in juvenile insulin-dependent diabetes, juvenile rheumatoid arthritis and celiac disease].

The heterozygous effect observed for the HLA and disease association in insulin dependent diabetes, juvenile rheumatoid arthritis and coeliac disease is interpreted in the view of recent cellular and molecular data of MHC class II molecules demonstrating the existence of hybrid HLA DQ molecules and conformational determinants created by Trans (or Cis) complementation. It is postulated that unique determinants created de novo by such mechanisms represent the structural basis for the altered immune response leading to the pathogenesis of these auto-immune diseases.

Alleles↗
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

T-lymphocyte progenitors in man: phenotypic characterization of blood and bone marrow T-colony forming cells.

Human T-lymphocyte cell precursors are driven to proliferate in vitro and to form T-cell colonies during incubation with a PHA-stimulated lymphocyte supernatant (P-SUP). By using cell affinity chromatography, we selected different populations of putative T-lymphocyte precursors in the blood and bone marrow. T-colony forming cells (T-CFC) were found in each of these different populations of cells with phenotypically immature cell surface markers: OKT11- cells or OKT4-/OKT8- cells in the blood and bone marrow, and OKT10+ or RFB-1+ cells in the bone marrow. Pretreatment with OKT3, together with a monoclonal anti-DR antibody and complement, did not abrogate the T-colony forming capacity. The OKT4-/OKT8- precursors were more radiosensitive (Do = 105 rads) than OKT4+, OKT8+ cells (Do = 360 rads) in their T-colony forming capacity. These results suggest that T-CFC could be induced to grow in agar from cells populations representing early steps of the T-cell lineage.

Aged↗
PubMed1985

Interferon-gamma modulates HLA class II antigen expression on cultured human thymic epithelial cells.

Cultures of human thymic epithelial cells (TEC) were tested for the expression of HLA class I (A, B, C) and class II (DR and DC) antigens by indirect immunofluorescence. The epithelial nature of the cells was proven by using an antikeratin antiserum. A high level of expression (close to 100% positive cells) of HLA class I antigens was observed on TEC at the beginning of the culture and remained unchanged for up to 12 days. In contrast, HLA class II antigen expression (85% DR+ and 75% DC+ cells on day 2) decreased gradually and reached very low levels (less than 5% DR+ or DC+) by day 7 of culture. This loss of class II antigen expression was not seen when cultures were performed in the presence of supernatants from activated T cells containing interferon-gamma (IFN-gamma). Furthermore, the presence of recombinant IFN-gamma (rIFN-gamma) in the medium from the onset of culture maintained HLA-DR and DC antigen expression on a high number of cells (comparable to that observed on day 2 of culture). A large percentage of rIFN-gamma-treated cells also showed intracytoplasmic HLA-DR antigen expression. Addition of rIFN-gamma at various times after the onset of the culture led to a reinduction of DR and DC antigen expression. This effect of rIFN-gamma was observed in 48 hr with concentrations as low as 10 IU/ml and was apparently specific for this IFN species, in that rIFN-alpha was unable to modify HLA class II antigen expression at concentrations up to 1000 IU/ml. The increased expression of HLA class II antigen was truly due to induction in individual TEC, rather than selection of class II-positive cells, because induction under the influence of IFN-gamma was reversible and occurred in the absence of proliferation in mitomycin-treated or gamma-irradiated cultures. Our results indicate that synthesis and membrane expression of class II HLA antigens are enhanced by IFN-gamma in TEC cultures. This finding raises the possibility that IFN-gamma participates in the mechanisms that assure the permanent expression of DR and DC antigens observed in TEC in vivo, with potentially important functional consequences in terms of education for self recognition.

Cell Survival↗
PubMed1984

Antigen-specific proliferative human T cell clones with specificity for diphtheria toxoid: genetic and molecular restriction by class II antigens.

Human T lymphocyte clones (TLC) specific for diphtheria toxoid (DT) were isolated from a DR6/7 individual by cloning in soft agar in vivo sensitized T lymphocytes. We report here the isolation and characterization of 3 of these clones by studying: (a) the kinetic of activation, (b) the surface phenotypes, (c) the fine specificity for one of the 2 DT chains and (d) the genetic restriction of the proliferative response by the haplotype DR7. Moreover, blocking studies of the proliferative response to DT by various immunochemically characterized anti-HLA-DR monoclonal antibodies indicate that, on the DR7 molecule, more than one Ia determinant may participate in the clonal DT proliferative response. By using human TLC of a defined specificity and well-characterized anti-DR monoclonal antibodies, such studies may help to define the functional repertoire of Ia molecules in man.

Clone Cells↗
PubMed1984

[Therapeutic leukapheresis in tricholeukocytic leukemia].

Therapeutic leukapheresis was performed in a patient with hairy cell leukaemia (100,000 WBC/mm3; 98 p. 100 hairy cells) without signs of hypersplenism. Twenty-five sessions were carried out in 12 weeks. A rapid and significant improvement was observed with the WBC falling to 25,000 WBC/mm3 with 70 p. 100 of hairy cells and the normalisation of the bone marrow biopsy. When these sessions were finished, splenectomy was performed in optimal conditions. This treatment would seem to be valuable in hairy cell leukaemia without severe hypersplenism. Long-term improvement may be hoped because hairy cells have a very short turnover rate.

Adult↗
PubMed1982

Analysis of DR-like molecules on a marmoset Epstein-Barr virus-induced cell line using a monomorphic anti-human HLA-DR monoclonal antibody.

Mouse anti-HLA D region-related (DR) monoclonal antibodies have been found to cross-react with peripheral blood leukocytes from one primate species, the common marmoset (Callithrix jacchus). Immunoprecipitates of radioactively labeled cells extracted from a marmoset Epstein-Barr virus-induced cell line were analyzed by one- and two-dimensional gel electrophoresis and compared with the DR antigens of a human lymphoblastoid B cell line. Two chains of estimated molecular weights of 34 000 (alpha) and 28 000 (beta), similar to the human alpha and beta chains, have been observed in marmoset immunoprecipitates. Additionally, a set of spots located in the same area as the set of invariant spots found in human HLA-DR antigens is shown by two-dimensional gel electrophoresis. Thus, cross-reacting anti-human HLA-DR monoclonal antibodies could be used to analyze the expression and the structure of marmoset DR-like antigens.

Animals↗
PubMed1982

An increase in peripheral blood Ia-positive T cells in Sjögren's syndrome correlates with a decrease in the autologous mixed lymphocyte response.

The defective autologous MLR was studied in Sjögren's syndrome (SS) in relation to Ia+ cells as determined by reactivity with a monoclonal anti-human Ia antibody. By indirect immunofluorescence, the percentage of Ia+ T lymphocytes was increased in nine of 15 patients. There was no correlation with clinical features or drugs. The percentage of Ia+ T cells in the non-T cell preparations was normal. An inverse correlation was found between the percentage of Ia+ T cells and the proliferative response to autologous non-T cells. Removal of Ia+ T cells enhanced both the autologous MLR and the allogeneic MLR. Thus Ia+ T cells contain suppressor cells in the MLR, but this may not be the sole explanation for the defective autologous MLR.

Adult↗
PubMed1981

Characterization of antigenic determinants on human myeloid colony forming cells with monoclonal antibodies.

Immunologic characterization of myeloid progenitor cells (CFUGM) provides a new dimension for identification and separation of this hemopoietic cell population from other cells within marrow and peripheral blood. Monoclonal antibodies against human anti Ia-like (HLA-DR) determinants and against T lymphocytes were utilized to more precisely define the cell surface antigenic structure of human CFUGM. Complement-mediated cytotoxicity testing demonstrated the presence of HLA-DR antigens and absence of a T lymphocyte antigen on the clonogenic CFUGM. Similar degrees of cytotoxicity were noted for B lymphocytes and CFUGM using anti HLA-DR monoclonal antibodies. Our studies with the anti T lymphocyte antibody suggest that T lymphocytes may be selectively removed from marrow cells without depletion of myeloid precursor cells.

Antibodies, Monoclonal↗