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Biomedical subjects

H M Dosch

Publications and source records attributed to H M Dosch.

At least 109 records · Page 6Linked to original sources
PubMed1980

Microtubule assembly and conanavalin A capping in lymphocytes: reappraisal using normal and abnormal human peripheral blood cells.

We have analyzed the assembly of microtubules and the distribution of concanavalin A(Con A)-receptor complexes in the same populations of human peripheral blood T and B lymphocytes. We hoped to resolve the prolonged controversy over the relationship of microtubules to Con A cap formation in lymphocytes and to explain the abnormally high spontaneous and colchicine-induced Con A capping that was observed recently in lymphocytes from a patient with an inherited form of severe combined immunodeficiency disease (SCID) characterized by total immunologic dysfunction despite normal numbers and distribution of T and B cells. The data establish that (i) microtubule disassembly is correlated with enhanced Con A cap formation on normal human lymphocytes; (ii) T and B cells differ significantly from each other and from circulating polymorphonuclear leukocytes with respect to their capping responses after exposure to colchicine; and (iii) there is an abnormal relationship of microtubule assembly to surface topography in the functionally defective SCID cells.

B-Lymphocytes↗
PubMed1980

Identification of Ia on a subpopulation of human T lymphocytes that stimulate in a mixed lymphocyte reaction.

The delineation of discrete subpopulations of human T lymphocytes has permitted preliminary analyses of the complex cellular network regulating the immune response in man. We previously showed that a subset of T lymphocytes, designated as theophylline-sensitive because of their inability to bind sheep red blood cells in the presence of the drug, are responsible for antigen-specific suppression or regulation in an in vitro plaque-forming cell assay. We now show that 25 to 45% of these theophylline-sensitive T cells were Ia-positive by immunofluorescence with a rabbit antiserum raised against purified B lymphoblast surface antigenic material. These data suggested that 4 to 7% of peripheral blood T cells carry Ia determinants. The presence of Ia determinants on this T cell subset was confirmed by gel analysis of radioiodinated surface material. Furthermore, in mixed lymphocyte culture, the theophylline-sensitive cells demonstrated HLA-D determinants and were 10-fold more potent stimulators than equal numbers of B lymphocytes. The presence of Ia determinants on these T cells indicates the expression of major histocompatibility complex-related regulatory gene products on a specific human T lymphocyte subpopulation.

Animals↗
PubMed1980

Polyclonal activation of human lymphocytes in vitro. I. Characterization of the lymphocyte response to a T cell-independent B cell mitogen.

The staphylococcal cell wall component protein A (SpA) and formalinized, Cowan I strain Staphylococcal organisms (STA) were compared with the lectins phytohemagglutinin, concanavalin A, and pokeweed mitogen for their ability to trigger proliferation of normal human lymphocytes, lymphocyte subpopulations, and cells from patients with primary immune deficiency diseases. SpA was found to be a potent T cell mitogen, very similar to the other lectins tested. It failed to stimulate purified non-T cells and peripheral blood lymphocytes from patients with different forms of severe combined immunodeficiency disease (SCID). STA, treated to prevent the leakage of soluble SpA during culture, exclusively stimulated non-T cells: the responding cell population was characterized to be E-rosette negative but positive for C3 receptors, surface Ia, a receptor for STA itself, and likely carried surface immunoglobulin. Normal responses to STA were found in patients with the adenosine deaminase-positive form of SCID. In 18 patients with humoral immune deficiency syndromes, the presence of STA responses was correlated with the presence of circulating, surface immunoglobulin-bearing cells. A commercial STA preparation was rendered B cell specific after reformalinization, a procedure that eliminated the shedding of soluble SpA under culture conditions.

Animals↗
PubMed1980

The expression of deoxyguanosine toxicity in T lymphocytes at different stages of maturation.

Different human T cell populations were assayed for susceptibility of DNA synthesis to inhibition by deoxyguanosine. T lymphocytes from the thymus were most sensitive to inhibition of proliferation by deoxyguanosine (90% inhibition at 10 microM deoxyguanosine). This exquisite sensitivity of thymocytes appeared related to an enhanced ability of these cells for uptake and phosphorylation of deoxyguanosine to deoxyGTP and by their reduced ability to degrade accumulated deoxyGTP. Compared to more mature T lymphocytes and B cells, thymocytes contained the highest level of the salvage enzyme deoxynucleoside kinase and the lowest level of the nucleotide degrading enzyme, 5'-nucleotidase. The present study suggests that the levels of these 2 enzymes can serve as differentiation markers, identifying T cells at various stages of maturation, and that the loss of sensitivity to deoxyguanosine toxicity may be a stepwise process. Further, a deficiency in purine nucleoside phosphorylase may preferentially interfere with T cell maturation at an intrathymic stage of T cell differentiation.

Cell Differentiation↗
PubMed1980

Polyclonal activation of human lymphocytes in vitro-II. Reappraisal of T and B cell-specific mitogens.

The capacity of the T cell mitogens phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM), and Staphylococcus protein A (SpA) to induce B cell proliferation and differentiation was compared with the B cell mitogen, formalinized Staphylococcus aureus (STA). Lymphocyte subpopulations from normal donors and patients with various immunodeficiency diseases were studied. In the presence of the T cell mitogens, irradiated T cells were capable of providing a helper cell activity that enabled co-cultured B lymphocytes to proliferate in response to these mitogens and to differentiate into IgM-secreting (direct) hemolytic plaque-forming cells (PFC). In the PFC response, radioresistant T-helper and radiosensitive T-suppressor cell activities could be demonstrated. T-suppressor cell activity outweighed helper activity only in nonirradiated co-cultures stimulated with Con A. Patients with severe combined immunodeficiency lacked mitogen-induced helper T cells, whereas patients with various forms of humoral immune deficiency were normal in this respect. These findings and the tissue distribution of the helper activity is aquired early in post-thymic T cell differentiation. The data suggest that experiments with cell lineage-specific lymphocyte mitogens should be considered in the context of more complex cell-cell interactions.

B-Lymphocytes↗
PubMed1979

Abnormal lymphocyte capping in a patient with severe combined immunodeficiency disease.

Despite the presence of normal numbers and distribution of T and B lymphocutes and normal levels of serum immunoglobulins, a five-month-old infant failed to show any evidence of T-cell or B-cell immunity. In trying to identify a specific membrane abnormality as a potential cause of the immunologic dysfunction, we examined the lateral mobility of the cell-surface receptor for concanavalin A. In contrast to normal cells, in which the receptor is distributed uniformly over the cell surface, the patient's lymphocytes showed an unusually high accumulation of concanavalin A receptors in surface caps. This capping abnormality appeared in both T and B lymphocytes and was exaggerated by colchicine, an inhibitor of microtubule assembly. These findings support the theory that plasma-membrane-cytoskeleton interactions have a role in the expression of specific immunity; the findings also identify new areas that should be considered in trying to understand the primary immunodeficiency diseases.

B-Lymphocytes↗
PubMed1979

Identification of two serum components regulating the expression of T-lymphocyte function in childhood myasthenia gravis.

We studied serums and cells from nine children with myasthenia gravis to determine whether there were alterations in the distribution or function of different T-lymphocyte subpopulations. The low numbers of E-rosette-forming T lymphocytes and their failure to respond to antigen by producing normal suppressor T cells were correlated with the presence of an IgG antibody directed toward the theophylline-sensitive T-cell subset; this activity could be blocked by d-tubocurarine. Incubation of normal T lymphocytes with serum from patients rendered the cells "myasthenia-like" when assayed for E-rosettes and for antigen-induced suppressor-cell function. A second, non-IgG factor found in patients' serums had activity like that of thymic hormone and induced T-cell maturation in normal bone marrow. This factor was not inhibited by d-tubocurarine; its activity was strongest in the two patients most severely affected, and it disappeared after thymectomy in both these patients. We conclude that in childhood myasthenia gravis there may be two independent serum factors; one an IgG antibody directed at a subset of T lymphocytes, blocked by d-tubocurarine and apparently unaffected by thymectomy, and the other a thymus factor that induces T-lymphocyte maturation.

Antigens↗
PubMed1979

Lithium: a modulator of cyclic AMP-dependent events in lymphocytes?

Theophylline, salbutamol, isoproterenol, and dibutyryl cyclic AMP inhibited E-rosette formation by human T lymphocytes and immunoglobulin M secretion from human plaque-forming B cells and augmented T-suppressor cell activity in three patients with agammaglobulinemia. Lithium chloride increased mitogen-induced lymphocyte proliferation and inhibited suppressor cell activity. In the presence of lithium, the effects of all the drugs except dibutyryl cyclic AMP could be prevented. The data suggest a role for lithium in the modulation of cyclic AMP-dependent events in lymphocytes. Its potential role as an inhibitor of suppressor cell activity warrants further attention.

Albuterol↗
PubMed1979

Selective toxicity of purine deoxynucleosides for human lymphocyte growth and function.

A role for the enzymes adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) and purine-nucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyl-transferase, EC 2.4.2.1) in the functional maturation of lymphoid cells has been revealed by the association of inherited deficiencies of these enzymes and profound immune deficiency. Previous studies have suggested that the selective toxicity for lymphocytes may be mediated by the accumulation of toxic deoxynucleoside metabolites, likely through the action of specific kinases enriched in lymphoid cells. In order to study possible mechanisms whereby lymphocyte function may be impaired in these disorders, we have studied the effect of nucleosides and their deoxy analogues on both T and B lymphocyte growth and function. In the presence of deoxyguanosine, there was marked inhibition of T lymphoblast growth, phytohem-agglutinin-induced cell proliferation, and T suppressor cell activity. T helper cell activity and the differentiation of B cells to an antibody-secreting stage were unaffected. Deoxyadenosine was much less inhibitory, but in the presence of an inhibitor of adenosine deaminase, its effects on lymphocyte growth and function were markedly potentiated. The addition of deoxycytidine prevented deoxyadenosine toxicity in all assays, whereas it only interfered with deoxyguanosine effects on T lymphoblast growth. These studies provide some initial understanding for the selective loss of specific lymphocyte functions in individuals with inborn errors of purine metabolism.

B-Lymphocytes↗
PubMed1979

Distribution of 5'-nucleotidase in human lymphoid tissues.

Low activity of 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) in T lymphoblasts may explain the marked sensitivity of this cell to deoxynucleotide accumulation when compared to B lymphoblasts. The relevance of such observations with cultured cells to the normal immune system requires the demonstration of similar differences in the 5'-nucleotidase activity of normal human lymphocyte subpopulations. Sheep erythrocyte (E) rosette-forming cells from normal thymus, tonsil, and peripheral mononuclear cells have 5'-nucleotidase activities of 1.7, 11.3, and 21.2 nmol/hr per 10(6) cells. Non-E-rosette forming cells from the peripheral blood or tonsil have 5'-nucleotidase activity comparable to the higher levels found in the peripheral E-RFC. Increased levels of 5'-nucleotidase activity may be a marker for post-thymic T lymphocytes. T lymphoblasts have 5'-nucleotidase activity similar to values demonstrated for E-RFC in thymus, whereas cultured B lymphoblasts have 5'-nucleotidase activity 15 times greater than that of T lymphoblasts. On the basis of these observations, the 5'-nucleotidase deficiency in congenital agammaglobulinemia has been reevaluated. In these patients the data indicate that peripheral E-rosette forming cells have the enzyme deficiency, demonstrating an abnormality of T lymphocytes in this disorder of immunoglobulin production.

Agammaglobulinemia↗
PubMed1979

Quantitation of human thymus/leukemia-associated antigen by radioimmunoassay in different forms of leukemia.

Using a radioimmunoassay, increased levels of a human thymus/leukemia-associated antigen (HThy-L) have been detected in leukemic cells and plasma from most patients with E-rosette-positive acute lymphoblastic leukemia (ALL) and a number of patients with E-rosette-negative ALL, acute myeloblastic leukemia (AML), acute monomyelocytic leukemia (AMML), and acute undifferentiated leukemia (AVL). Low levels of HThy-L have been demonstrated in white cells from patients with chronic myelocytic leukemia (stable phase) and in mononuclear cells from patients with chronic lymphatic leukemia. The relationship between HThy-L and differentiation of hematopoietic cells is discussed.

Acute Disease↗