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Biomedical subjects

R W Dutton

Publications and source records attributed to R W Dutton.

At least 109 records · Page 6Linked to original sources
PubMed1972

Inhibitory and stimulatory effects of concanavalin A on the response of mouse spleen cell suspensions to antigen. I. Characterization of the inhibitory cell activity.

The presence of concanavalin A (Con A) inhibits the immune response of mouse spleen cell suspensions to erythrocyte antigens, stimulates the incorporation of tritiated thymidine, and increases cell recovery. Con A also restores the depressed response of cell preparations treated to remove thymus-derived cells. The dose-response curve for all four effects shows peak activity at 2 microg/ml. The depressed in vitro response of spleen cell suspensions from adult thymectomized, irradiated, bone marrow-restored mice is also restored by Con A. Here the dose-response curve is quite different with activity over a much wider range of concentration. The restoration of thymus-derived cell-depleted cultures by Con A is inhibited by the addition of untreated, unirradiated, mouse spleen cell suspensions, but is not inhibited by untreated, irradiated cells. Small numbers of spleen cells that have been preincubated with Con A and washed will inhibit the response of fresh, untreated cells to antigen. If the mouse spleen cell suspensions are incubated for 24 hr before the addition of Con A, the response to antigen is no longer inhibited but is stimulated instead. The data are compatible with the hypothesis that there are at least two cell targets for the action of Con A. One cell, that mediates the inhibitor effect, is a short-lived, radiosensitive, thymus-derived cell. The other cell, that mediates the stimulating effect, cannot be identified from the data presented here but may also be of thymus origin on the basis of studies by other investigators.

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PubMed1971

Regulation of the immune response. I. Differential effect of passively administered antibody on the thymus-derived and bone marrow-derived lymphocytes.

The effect of passively transfered antiserum against sheep erythrocytes (SRBC) on the antigen stimulated increase of SRBC-specific plaque-forming cells (anti-SRBC-PFC) and SRBC-specific thymus-derived lymphocytes (SRBC-specific T-cells) in the mouse spleen was examined. A dose of antiserum which severely suppressed the development of anti-SRBC-PFC did not prevent the increase in SRBC-specific T-cells, as measured by their ability to cooperate in the in vitro response to trinitrophenylated (TNP) SRBC. It was shown that the insensitivity of these T-cells to antiserum could not be explained by their low antigen requirement as compared to that of PFC. In the in vivo response of mice to TNP-SRBC, antibody specific for TNP suppressed the appearance of both anti-TNP- and anti-SRBC-PFC. The presence of free SRBC specifically prevented the suppression of the anti-SRBC-PFC. These observations are consistent with opsonization by phagocytic cells as the primary means of the observed suppression of PFC development by antibody.

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PubMed1971

Immunoglobulins on the surface of thymus-derived cells engaged in the initiation of a humoral immune response.

Preculture treatment of normal spleen cells with antiserum against mouse kappa light chains and complement was found to inhibit in vitro responses of these cells to TNP and erythrocyte (carrier) antigens, primarily by elimination of a thymus-derived helper component required for the response. Spleen populations inactivated in this way could be reconstituted with irradiated, carrier-immune spleen cells or with carrier-educated thymus-derived spleen cells. The ability of helper populations (i.e. irradiated, carrier-immune spleen cells or carrier-educated thymus-derived spleen cells) to enhance the response of normal spleen cells to hapten was eliminated by pretreatment of the helper cells with anti-kappa serum and complement. No significant effect of anti-kappa and complement treatment on precursor cell populations in normal spleen or bone-marrow-derived spleen could be demonstrated. The data are interpreted as evidence for the presence of immunoglobulin components. The function of these molecules is not established but it would be reasonable to assume that they are involved in antigen recognition, on the surface of thymus-derived cells.

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PubMed1971

Immune response restoration with macrophage culture supernatants.

Depression of the in vitro immune response of mouse spleen cell suspensions to sheep erythrocytes by removal of macrophages can be reversed by the addition of supernatants from peritoneal macrophage cultures. Supernatant activity can be absorbed by the red cell antigen, and supernatant-treated red cells are stimulatory in the absence of macrophages or supernatant.

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PubMed1971

Radioresistance of the enhancing effect of cells from carrier-immunized mice in an in vitro primary immune response.

The in vitro primary response of mouse spleen cell suspensions to 2,4,6-trinitrophenyl(Tnp)-erythrocytes has been studied. The number of anti-Tnp plaque-forming cells that arise after antigenic stimulation in vitro is greatly enhanced by prior immunization in vivo with the carrier erythrocyte. The enhancement is antigen specific. The priming for an enhanced response can be elicited with very low antigen doses and is often apparent 24 hr after immunization. It is marked from day 3 to day 14. Spleen cells from carrier-primed mice will enhance the anti-Tnp response of normal cells when mixed cultures of the two cell populations are challenged with Tnp-erythrocytes in vitro. The carrier-primed cells mediating this enhancing effect are thymus derived. The development of the thymus-derived, carrier-specific cell population has been generally assumed to involve the antigenic stimulation of cell proliferation. It was, therefore, somewhat surprising to find that the enhancing effect of the carrier-primed cells, once they had been generated, is not inhibited by x-irradiation.

Animals↗
PubMed1970

Antigen receptor molecules: inhibition by antiserum against kappa light chains.

Rabbit antiserum against mouse kappa chains, the predominant class of light chains found in mouse immunoglobulins, inhibits the immune response in vitro of mouse spleen cells to erythrocyte antigens. The inhibition becomes irreversible if the mouse spleen cells are treated briefly with both antiserum to kappa chains and complement.

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PubMed1967

Immunization of dissociated spleen cell cultures from normal mice.

A culture system for cell suspensions from mouse spleens has been described. The system provides adequate conditions for in vitro immunization on initial exposure to heterologous erythrocytes. The in vitro response closely parallels that observed in vivo with respect to size, early kinetics, antigen dose, and the inhibitory effect of passive antibody. The response of cultured cells differs in two respects from that seen in vivo. There is an increase in the ability to discriminate between different varieties of homologous erythrocytes and the in vitro response does not appear to be limited by whatever mechanisms regulate the in vivo response.

Animals↗
PubMed1967

Cell populations and cell proliferation in the in vitro response of normal mouse spleen to heterologous erythrocytes. Analysis by the hot pulse technique.

The role of proliferation in the development of 19S antibody-forming cells in the primary response has been investigated in an in vitro system. Spleen cell suspensions from normal, unimmunized mice were cultured in vitro in the presence of mammalian erythrocytes and the number of 19S hemolytic plaque-forming cells that arose 4 days later was measured. The hot pulse technique for the selective irradiation of those cells which synthesize DNA during a defined period of time has been described. The effect of such hot pulses administered at various times after the addition of antigen on the subsequent appearance of antibody-forming cells was determined. The results established that: (a) the onset of DNA synthesis does not start for approximately 24-32 hr after the addition of antigen, (b) essentially all the antibody-forming cells arise by cell division, and (c) different cell populations are involved in the response to two non-cross-reacting antigens.

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PubMed1966

Immunization of normal mouse spleen cell suspensions in vitro.

Dissociated cells from the spleens of unimmunized mice were cultured with and without various mammalian erythrocytes. Spleen cell suspensions cultured with heterologous red cells developed levels of hemolytic plaque-forming cells only one log(2) less than those seen in vivo. The reaction is specific for the in vitro immunizing erythrocytes. Antibody was demonstrated in the culture fluids.

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