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Biomedical subjects

G Corte

Publications and source records attributed to G Corte.

At least 55 records · Page 3Linked to original sources

The same human alloreactive T cell clone can help both B lymphocytes and specific cytotoxic precursors.

Human alloreactive proliferating T cell clones have been compared for their capacity to provide help for B cell activation and the generation of a specific cytotoxic response. The results demonstrate that, when triggered by the relevant alloantigen, the same T cell clone can induce a strong polyclonal B cell activation and serve as the only source of helper cells for the generation of a specific cytotoxic response by any source of CTL precursors against any stimulator cell present in culture.

B-Lymphocytes↗

Differential tissue distribution and ontogeny of DC-1 and HLA-DR antigens.

The tissue distribution and the ontogeny of DC-1 antigens have been investigated and compared with those of HLA-DR antigens. Indirect immunofluorescence (IIF) staining of surgically removed normal tissues from adults with the monoclonal antibody (MoAb) BT3.4 has detected DC-1 antigens in tissues of various embryologic origin. The tissue distribution of DC-1 antigens is more restricted than that of HLA-DR antigens, as the former are not detected in duodenal epithelium, colon mucosa, and ductal mammary gland epithelium. In fetuses up to 26 weeks of age, DC-1 antigens were detected only on cortical and medullary thymic dendritic cells with an anatomic distribution similar to that of reticuloepithelial cells and in endothelial cells of the small intestine. At this stage of intrauterine life, HLA-DR antigens have already reached their full tissue distribution. The tissue distribution and the ontogeny of DC-1 antigens resemble those of their murine counterparts, i.e., the I-A antigens.

Adult↗

Pulmonary sarcoidosis: excess of helper T lymphocytes and T cell subset imbalance at sites of disease activity.

Different lymphocyte subpopulations have been evaluated in bronchoalveolar fluid and blood obtained from six patients with active and six with inactive pulmonary sarcoidosis and from six normal subjects by means of two recently described monoclonal antibodies, 5/9 and MLR4. The percentages of OKT4 positive (helper) and OKT8 positive (suppressor) T cells were also determined. Patients with active sarcoidosis had significantly higher proportions of 5/9 positive T cells in the bronchoalveolar fluid than patients with inactive disease (p less than 0.01) or normal subjects (p less than 0.001). In contrast, the proportions of 5/9 positive blood T cells were similar in the three groups studied. Patients with active sarcoidosis had also a greater proportion proportion of MLR4 positive T lymphocytes in bronchoalveolar fluid than patients with inactive disease or normal subjects (p less than 0.01 for each comparison), but similar proportions of MLR4 positive blood T cells were found in each group. The ratio of 5/9 positive to MLR4 positive T cells was higher in the bronchoalveolar fluid (but not in the blood) in patients with either active or inactive sarcoidosis than in normal subjects. These observations suggest that the MLR4 negative fraction rather than the MLR4 positive fraction of the 5/9 positive T cells is preferentially expanded in the lungs of patients with pulmonary sarcoidosis and may indicate a secondary role for the MLR4 positive T cells in producing lung injury in this disorder. Comparisons of the OKT4 positive and 5/9 positive T cells showed that in patients with active disease most of the lung T lymphocytes expressed both the OKT4 and the 5/9 surface antigens, so the 5/9 monoclonal antibody may be considered a good marker of activity in this disorder. Pulmonary sarcoidosis may be characterised by the preferential expansion of helper T cell subsets at sites of disease activity.

Adult↗

Distinct HLA-DR epitopes and distinct families of HLA-Dr molecules defined by 15 monoclonal antibodies (mAb) either anti-DR or allo-anti-Iak cross-reacting with human DR molecule. I. Cross-inhibition studies of mAb cell surface fixation and differential binding of mAb to detergent-solubilized HLA molecules immobilized to a solid phase by a first mAb.

A series of HLA-DR-reactive mouse anti-human B cell or anti-Ia monoclonal antibodies (mAb) have been used to explore the serological complexity of human class II antigens at the determinant level, using two techniques: (a) cross antibody-binding competitor assays using 125I-labeled and-unlabeled mAb were performed to study the topological organization of the corresponding determinants to determine epitopic clusters recognized by this collection of mAb and (b) differential reactivity of mAb to detergent-solobilized solid-phase-immobilized HLA-DR molecules to determine epitopes expressed on identical DR isotypes. The fifteen mAb could be classified according to the first technique as falling into three different epitopic clusters. Using the second technique, we were able to define at least two independent molecular subsets, one co-expressing two of the three epitopic clusters and the second expressing only the third one. We could not formally identify molecular subsets expressing only one of the first two clusters, using the second technique. The precise serological mapping of the determinants recognized by various anti-class II mAb should prove very useful if such mAb were to be introduced in anti-class II-specific T cell clone blocking experiments. We anticipate that some of them should facilitate the correlation at the clonal level between the T cell repertoire and the epitopes or molecular subsets defined by these mAb. However, within mAb belonging apparently to a same cluster, some could mediate different biological effects.

Animals↗

Circulating T-cell subsets in Graves' disease: differences between patients with active disease and in remission after 131I-therapy.

In the present investigation some surface markers in peripheral blood T lymphocytes of patients with active Graves' disease and subjects in remission after 131I-therapy have been studied. We confirmed low TG levels in untreated patients and normal values in treated subjects. Increased percentages of DR+, MLR4+ (activated T cells), and 5/9+ (inducer-helper) T cells were detected in patients with active disease, thus indicating the presence of activated T cells and suggesting increased levels of helper T cells. High percentages of MLR4+ and 5/9+, but normal levels of DR+ were found in 131I-treated subjects. The different distribution of DR and MLR4 positivities on 5/9+ and 5+9-T cells confirm the different meaning of these two markers of the activation state. The imbalance of T-cell subsets found in 131I-treated subjects and the normal values observed in patients with hyperthyroidism due to toxic adenoma indicate that hyperthyroidism per se is not sufficient to explain the T-cell alterations. The possible meaning of these findings is discussed with respect to previous hypotheses on the pathogenesis of Graves' disease.

Adult↗

Microfingerprinting analysis of human Ia molecules favours a three loci model.

Alpha subunits from DC1 Ia molecules, when compared with DR alpha subunits, are shown to possess distinctive features revealed by differences in microfingerprinting patterns after peptic digestion. Alpha chains from BR4X7 molecules differ from DC1 alpha chains and are more similar to DR alpha chains. Since DC1 and BR4X7 beta chains (which carry the HLA-controlled alloantigenic determinants) associate with different alpha subunits, it is considered unlikely that they are controlled by alleles at the same locus. The proposed model implies the existence of three tightly linked HLA loci controlling the beta subunits of DR, DC and BR molecules respectively.

Alleles↗

Defect of T helper lymphocytes, as identified by the 5/9 monoclonal antibody, in patients with common variable hypogammaglobulinaemia.

Peripheral blood lymphocytes from 17 patients with common variable hypogammaglobulinaemia (CVH) were tested for reactivity with the 5/9 monoclonal antibody which reacts with about 15% of normal T-PBL in which all helper activity is found. In PBL from CVH patients, the proportions of OKT4 and OKT8 positive cells were also determined. Five patients had normal percentages of 5/9 cells and a normal OKT4/OKT8 ratio. Twelve patients had significantly decreased (or absent) 5/9 lymphocytes. Among these, five had decreased 5/9 cells and a normal OKT4/OKT8 ratio and seven had decreased 5/9 cells and an inversion of the OKT4/OKT8 ratio. The deficiency of the helper phenotype T cell subpopulation identified by the 5/9 monoclonal antibody in many patients with CVH may be relevant in the pathogenesis of this disease.

Adolescent↗

Can heterologous collagen enhance the granulation tissue growth? An experimental study.

A purified and lyophilized sponge of native bovine tendon collagen (Gelfix) was used to plug gastric, jejunal and colonic surgical holes (phi = 6 mm) on 78 white rats. In a control group (18 rats) colonic holes were plugged with autologous epiploon. The mortality rate due to generalized peritonitis, was higher (Fischer test = 4%) in the control group than in animals treated with the heterologous collagen. The healing process was evaluated by light microscopy at sequential intervals ranging from 4 to 120 days after implantation. The heterologous collagen biological activity was evaluated as follows: 1. The sponge was labelled with Tyrosine 125I or mixed with Collagen Methyl 14C methylated. Then the radioactivity of the isolated granulation tissue cells was evaluated. The electrophoresis of these lysed cells, as well as histoautoradiography were performed. 2. Indirect immunofluorescence studies employing rabbit antibodies against fibronectin were also carried out. The heterologous collagen seemed to act as a mechanical support and as a stimulus to chemotactic migration of fibroblasts. It also appeared to participate as a nutrient substitute in the metabolic activity of the granulation tissue. Finally, heterologous collagen fibers were found to be massively bound by fibronectin.

Animals↗

A monoclonal anti-DC1 antibody selectivity inhibits the generation of effector T cells mediating specific cytolytic activity.

The products of the DC locus have been shown to be structurally different from those of the DR locus. In this paper it is shown that, unlike anti-DR antibodies, a monoclonal antibody directed against DC1 does not affect proliferation of T cells in response to alloantigens or soluble antigens or production of Ig in a pokeweed mitogen-stimulated in vitro culture. However, the anti-DC1 inhibits the generation of effector T cells mediating specific cytolytic activity, whereas no inhibitory effect can be observed on natural killer and antibody-dependent cytotoxic cell activities.

Antibodies, Monoclonal↗

Demonstration at the single-cell level of the existence of distinct clusters of epitopes in two predefined human Ia molecular subsets.

The expression at the cell surface level of two previously defined human Ia antigen subsets, NG1 and NG2, was studied. Two monoclonal hybridoma antibodies, D1-12 (anti-NG1) and D4-22 (anti-NG2), labeled with distinct fluorochromes, were used as probes. The results indicate that NG1 and NG2 molecules are simultaneously expressed on the same cell, and moreover, that they are identifiable as spatially separate structures. In addition, when a series of 6 other anti-Ia monoclonal antibodies previously described were analyzed in a checkerboard test of binding inhibition at the cell surface level, they were found to closely mimic the reactivity pattern of either D1-12 or D4-22 antibody, suggesting that NG1 and NG2 Ia subsets express independent clusters of highly immunogenic epitopes.

Antibodies, Monoclonal↗

Phenotypic and functional characterization of a Sézary cell.

We have studied the surface antigen pattern, enzymatic phenotype, and functional capacity of peripheral blood lymphocytes from a patient with Sézary syndrome (SS). The majority of these cells formed E rosettes but lacked the Fc(mu) receptor. The neoplastic cells were reactive with pan-T cell (OKT3)- and helper T cell (OKT4)-subset monoclonal antibodies; however, they lacked the 5/9 antigen, which identifies a more restricted subset of helper T cells. Most SS cells also reacted with PTF 29.12, a monoclonal antibody which recognizes DR determinants. Only 35% of the cells expressed single, focal accumulations of alpha-naphthyl-acid esterase activity, which is a characteristic of T.M cells, but 85% of them showed this focal staining pattern with acid phosphatase or beta-glucuronidase. Mononuclear cells from the SS patient showed poor or no proliferative response to phytohemagglutinin, pokeweed mitogen, concanavalin A, purified protein derivative, Candida, and allogeneic cells and lacked both helper and suppressor activity for pokeweed mitogen driven production of IgM and IgG immunoglobulins by normal B cells, but they were able to stimulate a marked proliferative response in mixed-lymphocyte culture. The defective expression of enzymatic and surface membrane characteristics, together with the lack of some T-cell functions, suggests that the patient cells may be immature T.M lymphocytes.

Aged↗

Human T cell subpopulations defined by a monoclonal antibody. I. A small subset is responsible for proliferation to allogeneic cells or to soluble antigens and for helper activity for B cell differentiation.

A monoclonal antibody (5/9) was obtained that reacts with the majority of alloactivated human T cells but only with 15 to 20% peripheral T cells. The populations reactive with the 5/9 antibody were separated from the remaining T cells by rosetting techniques using 5/9-coated ORBC. 5/9+ and 5/9- populations were analyzed for different in vitro activities. The helper activity of PWM- driven B cell differentiation appeared to be restricted and highly enriched in the 5/9+ population. In addition, 5/9+ cells contained all the cells capable of proliferation to tetanus toxoid and allogeneic cells. Thus, in vitro activities commonly used for evaluation of T cell function seem to be confined to a small fraction of peripheral T cells.

Animals↗

Human T cell subpopulations defined by a monoclonal antibody. II. Evidence for cell cooperation in the response to alloantigens and generation of cytolytic cells.

It has been shown previously that the 5/9 monoclonal antibody defines a small T cell subpopulation in human peripheral blood that includes all the cells responsible for proliferation to tetanus toxoid and to alloantigens as well as the helper cells for B cell differentiation. In the present study, human peripheral blood T cells were fractionated according to their reactivity with the 5/9 monoclonal antibody and stimulated in mixed lymphocyte culture (MLC). In spite of a strong proliferative response in MLC, 5/9+ cells generated no cytolytic activity against PHA-activated lymphocytes bearing the stimulating alloantigens (CTL activity) or against the K562 human cell line (NK activity). The precursors of these cytolytic effector cells were present in the 5/9- fraction. However, 5/9+ cells or soluble factors derived from 5/9+ cells were needed to induce 5/9- cells to respond in MLC and develop cytolytic activity. Both 5/9+ and 5/9- cell populations, upon MLC stimulation, were able to lyse L1210 mouse lymphoma cells in the presence of specific antibodies (ADCC).

Animals↗