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Biomedical subjects

L Lindholm

Publications and source records attributed to L Lindholm.

At least 163 records · Page 9Linked to original sources
PubMed1976

Suppressor cell activity in a male infant with T-and B-lymphocyte dysfunction treated with thymosin.

A male infant with bilateral iris coloboma who had had repeated infections and malabsorption was studied. The levels of total lymphocytes and of T and B cells were normal or high, but IgA became undectable and IgG low, whereas IgM was normal. His lymphocytes did not respond to phytohemagglutinin (PHA), concanavalin A, pokeweed mitogen (PWM) or in mixed lymphocyte reactions (MLR), nor did they respond in vitro when thymosin was included in the test systems. He was skin-test-negative, even to dinitrochlorobenzene. His crudely isolated T lymphocytes and the supernatant of his PHA-stimulated lymphocytes inhibit the response of normal lymphocytes to PHA, PWM, and in MLR. During thymosin treatment skin test and lymphocyte reactivity to mitogen remained negative. He became faintly positive in MLR, and the suppressor activity in the supernatant of his PHA-stimulated lymphocytes no longer inhibited the response of normal lymphocytes to PHA, PWM, or in MLR. In parallel with thymosin treatment he showed quite marked clinical improvement.

B-Lymphocytes↗
PubMed1976

T lymphocytes in atopic children.

The number of circulating T and B cells and the sensitivity of lymphocytes to stimulation with phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweek mitogen (PWM) was studied in 233 atopic children. The number of T lymphocytes was found to be decreased in cases of rhinoconjunctivitis, asthma as well as atopic eczema. Levels of B lymphocytes were normal. Sensitivity to stimulation with PHA and to a lesser degree, Con A, was significantly decreased whereas stimulation with PWM was unaffected. The severity of the atopic eczema was inversely correlated to T cell numbers. Several lines of evidence indicated that the abnormalities observed were intrinsically associated with the atopic conditions and not evoked by corticosteroid treatment. The results are compatible with the hypothesis that atopy is associated with a defect of a subpopulation of T cells. The possibility that this subpopulation has a suppressor function on reagin formation is discussed.

Adolescent↗
PubMed1976

Interaction of cholera toxin and toxin derivatives with lymphocytes. II. Modulating effects of cholera toxin on in vivo humoral and cellular immune responses.

The in vivo effects of cholera toxin on lymphoid organ structure and function in mice were investigated. It was found that within a day following intravenous injection of 1 mug of toxin, thymus as well as spleen weight decreased but the animals remained healthy. Histological studies suggested that the involution of lymphoid organs was due to cell death. Injection of cholera toxin into adrenalectomized mice was lethal within 36 h. In these animals no decrease in lymphoid organ weight was noted. Thymus cells from toxin-treated mice were found to be much inferior to thymocytes of untreated animals in their in vitro response to Concanavalin A, whereas the response of spleen cells from toxin-treated animals to mitogens was slightly increased. 1 mug of cholera toxin increased primary antibody formation when given to mice together with antigen (sheep erythrocytes) and decreased primary antibody formation when given before or after the antigen. The toxin also increased secondary antibody formation when injected simultaneously with or after the booster antigen dose, and decreased the antibody formation when given a few days before the booster injection. Treatment of mice with toxin was found to increase the capacity of spleen cells from these animals to induce the parental effect on antibody formation and to induce graft-versus-host reactions. The mechanisms behind the observed effects are discussed. It is suggested that cholera toxin affects different types of cells involved in immune responses primarily by a direct inhibitory action on cellular proliferation but also indirectly by causing release of adrenal gland hormones.

Adrenalectomy↗
PubMed1976

Cholera toxin, ganglioside receptors and the immune response.

Cholera toxin activates plasma membrane adenylate cyclase in all mammalian cell types. The structure-function relationship of the toxin has recently been clarified, and the cell membrane receptor identified. This information has made cholera toxin the "agent of choice" for studies in many biological systems of the possible regulatory role of adenylate cyclase/cyclic AMP. This article describes briefly our current knowledge about the toxin and its receptor. It then reviews recent research which has revealed that cholera toxin has strong modulating influences on the proliferation of normal and malignant lympocytes as well as on the initiation and expression of immune responses. The toxin has been found to inhibit DNA synthesis of B and T lymphocytes in vitro without inducing cell death and also to inhibit seems to decrease antibody secretion from plasma cells in vitro, and might also interfere with the release of other soluble immunological mediator subtances. In vivo cholera toxin induces a transient involution of the spleen and a more prolonged lymphocyte depletion of the thymus in mice; these effects appear to be mediated through the adrenal glands. The toxin inhibitors allograft rejection, and either stimulates or suppresses antibody formation depending on the timing of the toxin in relation to the antigen administration. It increases the capacity of the spleen cells to induce graft-vs-host reactions and the "allogeneic effect" on antibody production. An inhibitory effect on a normal suppressor population among the spleen cells has been identified. The findings illustrate the complex effects induced on the immune system by the probably most discriminative investigative tool available for stimulation of the adenylate cyclase/cyclic AMP system.

Animals↗
PubMed1974

Interaction of cholera toxin and toxin derivatives with lymphocytes. I. Binding properties and interference with lectin-induced cellular stimulation.

The interaction of cholera toxin and a number of toxin derivatives, containing different proportions of light and heavy toxin-composing subunits (L and H), with mouse lymphocytes was studied. Experiments with [(125)I]toxin showed that a single cell can rapidly, within minutes, bind up to 40,000 molecules of toxin, the association constant was estimated to 7 +/- 4 x 10(8) liters/mol, and binding was found to be very similar at 37 degrees C and 5 degrees C. Immunofluorescence studies revealed that the toxin attachment is located on the cell surface, and that purified L subunit but not H subunit binds to the cells. A natural cholera toxoid, built up by aggregated L subunits, showed almost identical binding properties as toxin to the cells. Pure G(M1) ganglioside, the proposed membrane receptor structure for toxin, prevented entirely the cellular binding of both toxin and toxoid. Cholera toxin in concentrations down to approximately 5 x 10(-11) mol/liter (corresponding to 10 bound molecules/cell) inhibited thymus cells from being stimulated to DNA synthesis by concanavalin A (con A), and spleen cells from such stimulation by phytohemagglutinin. The G(M1) ganglioside but not a series of other pure structurally related gangliosides and neutral glycosphingolipids neutralized this toxin activity. Toxin derivatives which, in similarity with toxin, possessed H as well as L subunits but in other proportions, were potent inhibitors of con A-induced thymocyte stimulation, whereas the natural toxoid (aggregated L subunits), purified toxin L subunit and purified toxin H subunit were up to 300-fold less active on a weight basis. The capacity of cholera proteins to inhibit con A-induced thymocyte stimulation correlated well with their activity in the rabbit intradermal toxicity assay. The inhibitory action of cholera toxin on con A-induced thymocyte stimulation did not depend on decreased cell viability from the toxin treatment, nor was it caused by a reaction between toxin and con A. [(125)I]con A bound equally well to the cells when toxin was present as when it was absent, which proves that the toxin did not compete for cellular con A receptors. Nor did the toxin seem to disturb the general mobility of membrane receptors or their ability to accumulate in caps. It is concluded that the L type of subunit confers rapid and firm binding of cholera toxin to lymphocyte membranes, probably to G(M1) ganglioside receptors. For biologic activity the additional presence of H subunit is important. One manifestation of toxin action on lymphocytes is inhibition of lectin-induced DNA synthesis; probably this effect relates to the ability of cholera toxin to raise the levels of intracellular cyclic 3'5'-adenosine monophosphate.

Animals↗