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Biomedical subjects

G S Incefy

Publications and source records attributed to G S Incefy.

At least 37 records · Page 2Linked to original sources
PubMed1981

In vitro differentiation of human marrow T cell precursors by thymic factors in severe combined immunodeficiency.

Marrow cells from 16 patients with severe combined immunodeficiency diseases (SCID) were examined for the presence of T cell precursors which could be induced to express surface markers and functions of T lymphocytes after exposure in vitro to thymic extracts or peptides of thymic origin (thymopoietin and thymopoietin32-36 (TP-5). Marrow cells from 14 patients studied before transplantation revealed three patterns of response. In five patients, inducible T cell precursors were not detected. In six patients, precursors were detected which could be induced to express a human T lymphocyte antigen (HTLA) but acquired little or no ability to rosette with sheep erythrocytes (SRBCs). Induction of HTLA-positive and E rosette-positive lymphocytes was normal in only two patients, both of whom were engrafted with maternal lymphocytes as an apparent result of an intrauterine infusion. Induction of mixed leukocyte reaction (MLR) responses following exposure to thymic hormones was also observed in one of these two patients. In no case could significant responses to mitogens be elicited. Following transplantation, marrow cells from fully engrafted, immunologically reconstituted patients could be induced to bear HTLA, to form E rosettes, and to respond to mitogens and allogeneic cells following exposure to thymic extracts, thymopoietin, or TP-5. Thus, most patients with SCID manifest differentiative abnormalities intrinsic to lymphoid precursors which are corrected following engraftment of functioning allogeneic lymphoid precursors from normal donors.

Antigens, Surface↗
PubMed1981

Lymphocyte transformation induced by autologous cells. XI. The effect of age on the autologous mixed lymphocyte reaction.

The autologous mixed lymphocyte reaction (MLR) was lower in newborn infants and healthy subjects over 65 years of age than in adults between the ages of 20 and 32. In contrast, the allogeneic MLR, although impaired in newborn infants, was normal in elderly subjects. The degree of impairment of the autologous MLR in elderly subjects was correlated with the impairment in the response of lymphocytes from elderly subjects to phytohaemagglutinin (PHA) and Staphylococcus aureus proteins A (SPA). The percentage of autorosetting T cells and of T cells with the OKT4 phenotype was increased in elderly subjects. These findings are paradoxical as autoreactive T cells in young adults have been reported to be drawn from these two T-cell subpopulations.

Adult↗
PubMed1980

Induction of differentiation in human marrow T cell precursors by the synthetic serum thymic factor, FTS.

The serum thymic factor, 'facteur thymique serique' (FTS), was analysed in vitro for its ability to induce differentiation of normal human marrow T cell precursors into cells with T lymphocyte characteristics. FTS has been isolated, characterized, sequenced and synthesized. In the mouse, natural and synthetic FTS have similar activities in vitro in the rosette inhibition assay. Both substances influence a variety of T cell differentiation markers and functions in vivo. In this study, we found that synthetic FTS induced appearance of two T cell surface markers, HTLA phenotypes and the ability to form E rosettes, on a selective population of normal human marrow cells sedimenting in layers II or III of a Ficoll discontinuous density gradient. In addition, a population of lymphoid cells also found in layer III, which bears receptors for peanut agglutinin (PNA), was decreased in number following exposure to FTS. In the same gradient layer, cells which expressed terminal deoxyribonucleotidyl transferase (TdT) activity showed decreased activity after treatment with FTS. Functional activities characteristic of T lymphocytes were also enhanced in marrow cells of gradient layer III after preincubation with FTS. These T cell functions were demonstrated in marrow cells by their ability to respond and to stimulate allogeneic peripheral blood lymphocytes (PBL) in mixed lymphocyte reactions and by responses to phytomitogens, PHA, Con A and pokeweed. These changes were not observed in marrow cells of gradient layers I, IV and V or after incubation with an FTS analogue that lacked biological and antigenic activity in the mouse system.

Antigens, Surface↗
PubMed1977

Thymic activity in severe combined immunodeficiency diseases.

Thymic function was evaluated by quantitation of circulating thymic factor in patients with several forms of severe infantile immunodeficiency diseases. Direct quantitation of thymic factor in serum of patients with severe combined immunodeficiency revealed heterogeneity of this syndrome by this parameter, as was also shown by study of susceptibility of the marrow cells to differentiation in vitro. Thymic factor was not detectable in one patient with severe combined immunodeficiency, but was present in normal or near-normal concentrations in three others. Circulating levels of this hormonal activity were also not detectable in a patient with DiGeorge athymic syndrome. Following marrow or fetal liver transplantation, which corrected the severe combined immunodeficiency thymic factor levels either increased slightly or did not change appreciably. Fetal thymic transplantation, which together with fetal liver transplantation corrected the immunodeficiency in one patient with severe combined immunodeficiency, was associated with increase of thymic factor to normal levels. Fetal thymus transplantation alone, which was employed to correct the immunodeficiency of DiGeorge athymic syndrome, caused an increase in thymic factor activity to normal or near normal levels in this patient.

Bone Marrow Cells↗
PubMed1977

Rationale for combined use of fetal liver and thymus for immunological reconstitution in patients with variants of severe combined immunodeficiency.

Bone marrow cells from a patient with severe combined immunodeficiency were studied in vitro for thymus-dependent lymphocyte (T cell) differentiation by using, at varying times, thymic epithelial monolayers and culture supernatants, thymopoietin, ubiquitin, and thymic extract as inducing agents. On initial evaluation, with thymopoietin or human thymic extract, only a partial differentiation of marrow cells was achieved into cells bearing the human T cell antigenicity without the capacity to form rosettes with sheep erythrocytes, suggesting that the stem cells were defective. Two fetal liver transplantations aimed at reconstitution were unsuccessful, despite evidence of chimerism. Induction studies at that time demonstrated rosetting capacity (with sheep erythrocytes) of the patient's bone marrow cells after coculture with thymic epithelial monolayers but not with their supernatants. An 18-week fetal thymus (irradiated) was then transplanted, but the transplantation was unsuccessful and no clear evidence of chimerism was demonstrated. Subsequently, transplantation of another fetal liver resulted in chimerism and immunologic reconstitution. Serum thymic factor activity rose from 1:2 before transplantation to 1:16 after reconstitution. The combined use of fetal thymus and liver may provide effective immunological reconstitution in some variants of severe combined immunodeficiency.

Bone Marrow↗
PubMed1977

Induction of human granulocyte differentiation in vitro by ubiquitin and thymopoietin.

Human bone marrow cells were separated according to density by centrifugation on Ficoll-Hypaque gradients and then according to size by velocity sedimentation. This procedure resulted in fractions enriched for immature granulocytes, mature granulocytes, and lymphocytes. Cells in these fractions were analyzed for their expression of certain surface and functional differentiation markers and for their ability to respond to thymopoietin and ubiquitin with the expression of additional differentiation markers. A higher percentage of band form and segmented granulocytes than of more immature granulocytes expressed complement receptors on their surfaces. Thymopoietin and ubiquitin induced a significant percentage of the cells in the immature granulocyte fraction to express this marker. These data suggested that the complement receptor may be viewed as a differentiation marker on human granulocytes, the expression of which can be induced in vitro by thymopoietin and ubiquitin. Furthermore, fractions containing predominantly band form granulocytes were induced by ubiquitin (but not thymopoietin) to develop the capacity to respond to chemotactic agents, and cell fractions containing predominantly myelocytes and metamyelocytes were induced by thymopoietin and ubiquitin to develop the capacity to phagocytose latex particles. These findings indicated that thymopoietin and ubiquitin, two agents known to induce a number of stages of human and mouse lymphocyte differentiation, are also capable of inducing some stages of human granulocyte differentiation in vitro.

Binding Sites, Antibody↗
PubMed1976

The need for transcription and translation for differentiation of bone marrow cells by thymic factors in man.

1. Two small populations of human marrow cells are differentiated to cells bearing T-cell markers by Thymosin F3 or F5. 2. Analysis with metabolic inhibitors indicates that transcription and translation of RNA are needed for induction of T cell markers (layer III). 3. a) At 4 hours incubation RNA synthesis is enhanced in layers III, IV and V and inhibited in layers I + II. b) At 20 hours incubation RNA synthesis is markedly enhanced in all cell layers. 4. a) At 5 hours incubation protein synthesis is suppressed in layers I + II and III, but not in IV and V. b) At 20 hours incubation protein synthesis is markedly increased only in layer III.

Amanitins↗
PubMed1976

Aplastic anemia: presence in human bone marrow of cells that suppress myelopoiesis.

Bone marrow from a patient with aplastic anemia was shown by multiple criteria to have a block in early myeloid differentiation. This block was overcome in vitro by elimination of marrow lymphocytes. Furthermore, this differentiation block was transferred in vitro to normal marrow by coculturing with the patient's marrow. We suggest that some cases of aplastic anemia may be due to an immunologically based suppression of marrow cell differentiation rather than to a defect in stem cells or their necessary inductive environment.

Adult↗
PubMed1976

Human anti-T-cell cytotoxic sera as an approach to dissection of immunological systems.

The initial work on the analysis and differentiation of human lymphoid cells is described. Cells from various lymphoid organs and blood were used as the antigen to prepare various antisera. These antisera were then used to define the lymphocyte populations of patients with primary and secondary immunodefiency. They are also being used to begin the analysis of the differentiation of the T-lymphocyte.

Animals↗
PubMed1976

Antilymphocyte antibodies:an approach to dissecting the heterogeneity of the immune system.

Antilymphocyte antibodies can be used to dissect the lymphocyte populations and subpopulations. In the mouse, at least seven gene loci govern the expression of allo-, hetero-and autoantigens at the surface of T-lymphocytes. The antisera, especially the alloantisera, permit definition of the differentiative state of cells and discriminate between subsets of T-cells with different functions. Less is known about human T-lymphocyte differentiation antigens and their genetic determinism. However, heterologous antisera specific for human T-cells have been prepared and their use has been of help in studying this cell population. The antigens recognized by such antisera are present at a higher concentration on thymocytes than on peripheral blood T-lymphocytes. They appear at the surface of bone marrow T-cell precursors after a short incubation with thymic factors. Such markers of T-lymphocytes in various stages of differentiation and the study of in vitro differentiation from precursor cells have already proven to be valuable tools for clinical investigation, especially in the realm of immunodeficiency diseases.

Animals↗
PubMed1976

Heterogeneity of stem cells in severe combined immunodeficiency.

Two patients with severe combined immunodeficiency disease (SCID) having variable B-cell development have been shown to have marrow precursors of lymphoid cells which can be induced in vitro by thymic factors to express certain T-cell surface characteristics (HTLA+ phenotypes). Their marrow cells could not, however, be induced by these same factors to develop the E-rosette marker or functional activities of T lymphocytes. The marrow of these children also showed, when compared to that of normal adults, a different distribution of cellular elements on density gradient fractionation. The findings support the view that the disorder under study has a different pathogenesis from other forms of SCID previously analysed.

Age Factors↗