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Biomedical subjects

R W Dutton

Publications and source records attributed to R W Dutton.

At least 91 records · Page 5Linked to original sources
PubMed1977

Negative allogeneic effects in vitro. I. Allogeneic T cells markedly suppress the secondary antibody-forming cell response.

Murine T cells can mediate a potent negative allogeneic effect on the capacity of primed cells to develop the secondary antibody-forming cell response to hapten carrier in vitro. This effect is detected when T cells confront responding cells differing at the major H-2 locus. The allosuppression is relatively sensitive to mitomycin treatment and to irradiation. The T cells responsible for the inhibition of antibody formation appear to express the Ly2 but not the Ly1 alloantigen. The secondary response of spleen cells in culture is quite insensitive to positive allogeneic effects. The usefulness of this model in elucidating the mechanism of allosuppression and the relevance of such effects to studies involving genetic restriction on cell interactions is discussed.

Animals↗
PubMed1977

Negative allogeneic effects in vitro. II. Mapping of histocompatibility differences leading to allosuppression.

When splenic T cells from normal mice recognize alloantigens on primed spleen cells there is a dramatic suppression of the secondary antihapten PFC response of the latter cells. From studies using intra-MHC recombinants it appears that differences at K or D alone can elicit allosuppression. There is sometimes suppression to differences in the I region. Even small differences in H-2K, as seen in the H-2b mutants, are sufficient to lead to such negative allogeneic effects. Thus, as far as has been determined, the specificity of allosuppresive T cells is indistinguishable from that of cytotoxic effector cells. Negative allogeneic effects and positive allogeneic effects different in the degree to which they influenced the primary and secondary responses. In our experiments no evidence for positive allogeneic effects was seen in the secondary response to TNP-carrier even with cells differing at the I region only. In contrast the primary response to SRBC was much enhanced by allogeneic cells and little suppression of that response was seen. It is suggested that the allosuppression is distinct from cytotoxicity and may be a profitable model for the study of suppressor T cells.

Animals↗
PubMed1976

Separation of helper and suppressor T lymphocytes on a ficoll velocity sedimentation gradient.

A 5-20% Ficoll velocity sedimentation gradient has been successfully applied to separate concanavalin A (Con A)-induced helper; and suppressor T cells. When titrated into a constant number of fresh normal spleen cells responding to sheep erythrocytes, cells from the top pool show stimulatory effects while those from the bottom pool show inhibitory activity. Both activities are found to be Con A dependent and anti-theta sensitive. We conclude that Con A-induced helper and suppressor T cells are distinct subpopulations and such separation will allow further characterization of these cell types.

Antibody Formation↗
PubMed1975

Competition between concanavalin A-induced stimulatory and inhibitory effects in the in vitro immune response to antigen.

The humoral response of nude spleen cells (b cells) to sheep erythrocytes was measured in the presence of varying numbers of concanavalin A (ConA)-acvated stimulatory spleen T cells (helper) and Con A-activated inhibitory spleen T cells (suppressor) from BDF1 mice. It was found that suppressive effects could be reversed by the presence of additional numbers of stimulatory cells. These results seem incompatible with the hypothesis that suppression is mediated by supraoptimal numbers of stimulatory cells and provides additional evidence that separate populations of T cells mediate stimulation and suppression.

Animals↗
PubMed1975

The humoral response of mouse spleen cells to two types of sheep erythrocytes. II. Evidence for gene expression in the B lymphocyte.

There is multigene control of the response of mouse spleen cells to two types of sheep erytrocytes (H and L). Discriminator strains of mice make a much higher response to extra antigens found only on H SRBC than to the shared antigens found on both types of erythrocyte. Non-discriminator strains respond only to the shared antigens, making a responses as great as the discriminator response to the extra antigens. The cell type in which this genetic control is expressed was investigated by a number of methods for studying the role of the macrophage, T cell, and B cell in the production of anti-SRBC response. The results provide no evidence that the gene(s) operate at the macrophage, T cell, or any other accessory cell level. The data from B cell-limiting dilution experiments are compatible with genetic expression at the B cell level.

Animals↗
PubMed1975

The humoral response of mouse spleen cells to two types of sheep erythrocytes. I. Genetic control of the response to H and L SRBC.

Some strains of mice discriminate between two types of sheep erythrocytes (H or L-SRBC) and others do not. It is proposed that there are shared antigen(s) common to both H and L extra antig(s) present only in H. It shown that individual clones of antibody-forming cells make antibody to either the shared or extra antigens. These antigenic differences are not found to correlate with any of the known major sheep erythrocyte antigens. The genetic control of the ability to discriminate between these two types of red cell was investigated by an analysis of response of F1, F2 and backcross mice. The results suggest that the response is under multigene control. BL/6 mice give high responses to the extra antigens and low responses to the shared (high discriminator). DBA/2 gives high responses to the extra antigen (nondiscriminator). F1 mice give high responses to both extra and shared antigen but still discriminate between the two types of erythrocytes (low discriminator). Additional phenotypes appear in the F2 and backcross mice.

Animals↗
PubMed1975

Antigen suppression of the in vitro development of plaque-forming cells to autologous erythrocyte antigens.

Peritoneal cell cultures from NZB and C57BL/6 mice develop large numbers of PFC directed against antigens present on bromelain-treated isologous erythrocytes. The development of these autoimmune PFC can be suppressed by the addition of small numbers of BrMRBC at the start of the culture period. The possibility that the development of the plaque is prevented by the presence of antigen in vivo is discussed.

Animals↗
PubMed1975

The humoral response of mouse spleen cells to two types of sheep erythrocytes. III. A new VH region marker.

It was previously shown that there is multigene control of the response of mouse spleen cells to two types of sheep erythrocytes (H and L). Discriminator strains of mice make a much higher response to extra antigens found only on H SRBC than to the shared antigens found on both types of erythrocyte. Non-discriminator strains respond only to the shared antigens, making a response as great as the discriminator response to the extra antigens. In this study we have shown that the response to the extra antigen(s) on H SRBC is under the genetic control of a gene(s) located in the VH region near or to the left of the A5a, alpha 1, 3-dextran and NP makers.

Animals↗
PubMed1975

The properties of plaque-forming cells from autoimmune and normal strains of mice with specificity for autologous erythrocyte antigens.

Treatment of mouse erythrocytes with the proteolytic enzymes, bromelain, reveals antigenic determinants not normally exposed on the erythrocyte surface. It was found that not only NZB mice, a known autoimmune strain, but also several normal strains of mice contain cells in small numbers in their spleens and in larger numbers in their peritoneal cavities which will form plaques against bromelain-treated MRBC. During in vitro culture the number of anti-BR-MRBC PFC increases slightly in the spleen cell populations whereas the number of these PFC in peritoneal cells increases dramatically to as many as 100,000 PFC/10(6) cells. The plaques detected in this assay contain a central lymphoid cell and their development, which requires the presence of complement and protein synthesis, is inhibited by anti-mouse immunoglobulin.

Animals↗
PubMed1973

Inhibitory and stimulatory effects of concanavalin A on the response of mouse spleen cell suspensions to antigen. II. Evidence for separate stimulatory and inhibitory cells.

The addition of concanavalin A to mouse spleen cell suspensions can either inhibit or stimulate the immune response to heterologous erythrocytes according to the experimental conditions. Evidence is presented which is incompatible with the hypothesis that these two effects are mediated by a single cell and which favors the hypothesis of separate inhibitor and stimulatory cells.

Animals↗