David Eidinger

Antigenic Competition: A Review of Nonspecific Antigen-Induced Suppression

Publisher Summary The number of conflicting reports now exist on antigen-induced suppression suggests that no single hypothesis can be applied to this phenomenon. It is probable that the suppression observed is the end result of a heterogeneous group of phenomena varying with the antigens used, the experimental animal, and the time sequence of immunization. It is also possible that, at any particular time, more than one of these mechanisms is operative in the experimental animal. This chapter illustrates the progress that has been made in the past decade, especially with respect to the mechanism of antigenic competition, and makes an attempt to correlate the large amount of recent and diverse information in this field with current concepts of cellular immunology.

The heterocytotoxicity of human serum: I. Activation of the alternative complement pathway by heterologous target cells☆

Abstract Human serum induces cytolysis of mouse thymus and thymoma cells, and cytostasis of mouse bone marrow and spleen cells, and various methylcholanthrene-induced tumour cells. The latter was manifested by deficient metabolic activity when cultured in the presence of fresh human sera. Decomplementation procedures demonstrated that these heterocytotoxic effects are mediated in part via activation of the alternative complement pathway in human serum samples. The presence of properdin and C3 on the target cell surface was confirmed by immune adherence and indirect immunofluorescent tests. Activation of the alternative complement pathway was elicited by incubation of the human serum with the relevant target cells, resulting in the appearance of the cathodal migrating fragment of the factor B, denoting complement activation. The following publication will present evidence that activation of the alternative complement pathway takes place via an antibody-independent mechanism acting at the cell surface. These and other observations in the literature raise the possibility that activation of the alternative complement pathway by surface cell receptors on tumour cells represents a mechanism of natural immunity versus tumours.

The heterocytotoxicity of human serum. II. Role of natural antibody and of the classical and alternative complement pathways.

Abstract Mouse lymphoid cells and tumor cell lines were employed as target cells for the investigation of the mechanism of heterocytotoxicity in human serum samples. It was shown that the heterocytotoxic effects were due to two differing mechanisms. Cytotoxicity was mediated in part, by activation of the alternative complement pathway on target cell membrane, a process which was antibody-independent. A second mechanism of cytotoxicity was induced by natural antibodies to a target cell, which probably mediated activation of the classical complement pathway. These data may shed light on the frequently observed cytotoxicity in mammalian sera for various target cells.

Selective and opposing effects of cytochalasin B and other drugs on lymphocyte responses to different doses of mitogens

Abstract Drugs with pharmacologic activities on cell membrane components were tested for their effects on responses of murine lymphocytes to mitogens. The effects of the drugs were found to be partly selective and related to the type and dose of the mitogen. Most striking were the effects of cytochalasin B, which inhibited the responses to low doses of concanavalin A or phytohemagglutinin, but potentiated the reactions to the high doses of the lectins. Chloroquine and chlorpromazine, on the other hand, were more inhibitory to cultures containing supraoptimal doses of the lectins. Colchicine inhibited the responses against lipopolysaccharide more than those against the two lectins. The inhibitory effects of colchicine were almost unchanged when the drug was added at intervals up to 24 hr after the onset of culture, whereas the effects of the other tested drugs diminished markedly when added to cultures 6 hr or more after the mitogens. The results are discussed in view of their relationship to the poorly understood mechanisms which regulate the lymphocyte responses in the presence of different doses of mitogens.

The inhibition of murine lymphocyte mitotic responses by human and mouse sera. I. Evidence for a role of antibody-independent activation of the alternative complement pathway.

Abstract The responses of mouse lymphoid cell cultures to mitogens such as concanavalin A or antigen were inhibited by the addition of small amounts of fresh human serum. This inhibitory effect was reduced by specific decomplementation procedures such as heating at 50 °C to inactivate factor B or absorption with zymosan at 17 °C to deplete properdin from the serum. Human factor-B preparations reconstituted the inhibitory effect lost from human serum preparations heated at 50 °C. These findings are interpreted to indicate a fundamental role of activation of the alternative complement pathway (ACP) as an underlying mechanism of inhibition. Additional experiments designed to demonstrate a role of natural antibodies activating the classical complement pathway, while successful in these respects, also provided confirmatory evidence for an antibody-independent role of the ACP. Furthermore, data derived from experiments utilizing mouse sera tested on syngeneic mouse lymphoid target cells, were qualitatively similar to the results obtained employing human sera. The data suggest that the functional activities of mouse lymphocytes in vitro are inhibited by antibody-independent activation of the ACP, implying that this pathway may exercise a role in regulating lymphocyte function.

In vitro studies of 'antigenic competition'. I. The comparative responses of normal and 'immune' lymphoid cell populations.

Abstract A model has been presented for the mechanism of nonspecific antigen-induced suppression (“antigenic competition”) under in vitro conditions. The antigens used were Keyhole limpet hemocyanin (KLH) and horse erythrocytes, the former being injected into mice intravenously, and the latter being used as the antigen with which the spleen cells, derived from KLH-immune mice 2 days later, were cultured in vitro . It was observed that there was a specific and brief time interval after KLH injection during which suppression of the response to horse RBC in vitro occurred. The degree of suppression was proportional to the dosage of the first antigen, but independent of the dosage of the second. Suppression lasted for the duration of a 7-day period of culture, and was attributed to a decrease in antigen-reactive units specific for the horse RBC. These observations were discussed in the light of recent theories of antigen-induced suppression and antibody formation.