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P A Bretscher

Publications and source records attributed to P A Bretscher.

6 recordsLinked to original sources

In vitro induction of delayed-type hypersensitivity.

Murine spleen cells, cultured in vitro for 6 days in the presence of high concentrations of burro erythrocytes (BRBC), are sensitized to exhibit delayed-type hypersensitivity (DTH) specific for this antigen. Such cells, on being injected with antigen into the footpads of normal mice, cause a 24-h swelling reaction. This activity of the cultured cells requires the presence of BRBC both during the in vitro incubation and in the footpad. The activity of the sensitized cells in causing swelling is sensitive to anti-Thy-1 antibody and complement, and the kinetics of the swelling reaction are characteristic of a DTH response. In vivo low-dose priming of the spleen cell donors considerably enhances the ability of the cultured cells to cause swelling. This system provides a means of studying the regulation of the induction of DTH in vitro.

Animals

Requirement for antigen in lipopolysaccharide-dependent induction of B cells.

The magnitude of the IgM response to a variety of antigens, induced on the in vivo administration of lipopolysaccharide (LPS) to mice, is approximately proportional to the magnitude of the background response observed in untreated animals. This striking correlation suggests that the administration of LPS alone cannot in general induce a specific response in the absence of a background response. Such is the case for the antigen rat erythrocytes against which no LPS-dependent or background response is found. The response to a marginally immunogenic dose of rat erythrocytes, however, can be considerably enhanced by the administration of LPS. These observations are expected on the hypothesis that both background and LPS-induced responses are due to ongoing antigen-dependent stimulation in normal mice. This hypothesis is further supported by evidence suggesting that the LPS-dependent anti-sheep erythrocyte response is due, at least in part, to a particular antigen present on degraded mouse erythrocytes.

Animals

Helper T cells are required for the polyclonal stimulation of cytotoxic T cells by concanavalin A.

Concanavalin A stimulation of T-cell cytotoxicity has been shown to be absolutely dependent on helper T-cell collaboration. Thymocytes stimulated with ConA do not differentiate to yield cytotoxic effector cells. However, thymocytes cocultured with irradiated spleen cells as helpers and ConA yield high levels of cytotoxicity. The helper cell bears theta antigens on its surface, is not an adherent cell, and does not require any adherent cell functions in our culture conditions. The ConA-dependent helper cells appear to be polyclonal in specificity. Thus, polyclonal stimulation of cytotoxicity by ConA requires T helper-T precursor collaboration in analogy to antigen-specific T helper-T precursor interactions. Unlike the antigen-specific interacitons, the ConA-driven cytotoxicity does not appear to require linked associative recognition for induction of cytotoxicity.

Animals