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Biomedical subjects

D W Mason

Publications and source records attributed to D W Mason.

At least 55 records · Page 3Linked to original sources
PubMed1984

Experimental allergic encephalomyelitis: successful treatment in vivo with a monoclonal antibody that recognizes T helper cells.

Monoclonal antibody W3/25, which recognizes rat T helper cells, was injected i.p. or i.v. into Lewis rats with clinical signs of experimental allergic encephalomyelitis (EAE). This treatment, which was given 12 or 13 days after inducing EAE by the injection of purified myelin basic protein, significantly affected the course of the disease in that treated animals recovered, on the average, in 2 days, whereas control animals exhibited signs of EAE for a minimum of 4 days. Two pan-T cell monoclonal antibodies given in similar dosage failed to affect the course of the disease.

Animals↗
PubMed1983

MRC OX-22, a monoclonal antibody that labels a new subset of T lymphocytes and reacts with the high molecular weight form of the leukocyte-common antigen.

A mouse monoclonal antibody (MRC OX-22) is described that labels rat T cells which mediate graft-versus-host reactions and those responsible for the suppression of antibody synthesis in hosts undergoing these reactions. In contrast, most of the T cells that provide help for B cells are MRC OX-22 negative. These results, taken together with those published previously, demonstrate that the rat contains at least three phenotypically and functionally distinct subsets of T cells. The MRC OX-22 antibody also labels all B cells, 50% of bone marrow cells, but only 2% of thymocytes. Of these latter cells about half are found at the edge of the medulla and the remainder are randomly distributed throughout the cortex and medulla. These findings lend support to the view that mature thymocytes leave the thymus at the cortico-medullary junction, and also suggest that both cortex and medulla may be sites where thymocytes mature. Biochemical studies showed that the MRC OX-22 antibody reacts with the high molecular weight form of the leukocyte-common antigen (L-CA). Comparison with data on human L-CA suggests that the molecular and antigenic heterogeneity of this set of glycoproteins has been conserved between rat and man.

Absorption↗
PubMed1983

A spleen-thymus interaction is involved in the tolerization of thymocytes to xenogeneic erythrocytes.

Previous work has shown that thymocytes of rats receiving two i.v. injections, 4 days apart, of large numbers of xenogeneic erythrocytes become tolerant of the injected cells whereas peripheral T cells in the same recipients make a vigorous response to the injected antigen. Results are herein presented of experiments on the effect of splenectomy on the induction of thymocyte tolerance produced in this way. Splenectomy performed either immediately before the first injection of erythrocytes, or between the two injections, completely prevented tolerance induction and tolerance was still incomplete when splenectomy was performed as late as a few hours after the second injection of tolerogen. Sham splenectomy had no effect on the erythrocyte-induced thymocyte tolerance. The results demonstrate an essential role for the spleen in the tolerization of thymocytes in this system. Possible mechanisms and the implications for self tolerance are discussed.

Animals↗
PubMed1982

Induction of Ia antigen in rat epidermal cells and gut epithelium by immunological stimuli.

The expression of Ia antigen in rat keratinocytes and gut epithelium was found to be inducible by a variety of immunological stimuli. Graft-vs.-host disease (GvHD) was accompanied by the appearance of Ia antigen in both sites, whereas local immunological stimuli, such as a contact-sensitizing agent applied to the skin and Trichinella spiralis infection of the gut, caused the expression of Ia antigen confined to the sites of contact of these stimuli with the tissues involved. Both T helper and T cytotoxic/suppressor subsets of parental lymphocytes, used to produce GvHD in F1 hybrid recipients, induce Ia expression in the skin and gut of these hosts, but simultaneous removal of both subsets from the donor inocula prevented induction. The Ia antigen expression associated with GvHD was shown to be of host origin but was not acquired from bone marrow-derived cells. Attempts to detect Ia antigen in serum or lymph of rats with GvHD gave negative results, and it was shown that Ia+ cells in the lamina propria of the small intestine did not take up detectable amounts of Ia antigen from the Ia+ intestinal epithelium. It appears that the local recognition of antigen by T lymphocytes can result in the induction of Ia antigen in keratinocytes and in the epithelial cells of the intestine. This antigen is synthesized by the cells in which it is found, and the observation that immunological stimuli are responsible for its appearance suggests that its role is an immunological one. Failure to find evidence that the gut epithelium Ia antigen was transferred to lymph or taken up by other Ia+ cells in the intestinal villi supports the view that this Ia (and, by analogy, that found in keratinocytes) serves a local function, and the possibility that it is involved in antigen presentation to T cells is discussed.

Animals↗
PubMed1981

The toleration of rat thymocytes to xenogeneic erythrocytes: kinetics of induction and recovery.

The intravenous injection of large doses of xenogeneic erythrocytes into rats completely abrogated the ability of thymocytes from such animals to provide help for antierythrocyte antibody responses in an adoptive transfer system. Thymocyte tolerance developed at a time when the thymocyte donors were producing antibody to the tolerizing antigen, and spleen helper T cells were not tolerized by the injection protocol. A minimum of two injections of 1 ml of packed erythrocytes, spaced 4 - 5 days apart, was required to induce loss of helper activity. Tolerance was fully developed within 16 h of the last injection of antigen. Helper activity recovered over a 24-h period starting 5 days after this injection but could be delayed by giving further injections of antigen. These results suggest that the intrathymic pool of cells with assayable helper activity turns over in about one day and that precursors of this pool are probably also tolerable. Suppressor cells could not be detected in tolerant thymocyte populations indicating that the loss of helper activity was either a consequence of clonal inactivation or that an antigen-specific mechanism existed for the recruitment of helper cells from the thymus. The significance of these findings to the acquisition of self-tolerance is discussed.

Animals↗
PubMed1981

The rat mixed lymphocyte reaction: roles of a dendritic cell in intestinal lymph and T-cell subsets defined by monoclonal antibodies.

Cells present in the intestinal lymph of rats were obtained in large numbers by removing the mesenteric, portal and caecal lymph nodes and cannulating the thoracic duct 6 weeks later. About 1% of the cells present in the thoracic duct lymph of these mesenteric lymphadenectomized rats had striking dendritic morphology, were strongly Ia+ but labelled weakly with monoclonal antibodies that recognize rat B or T cells. It was found that intestinal lymph was highly enriched for cells that stimulated allogeneic T cells in the mixed lymphocyte reaction (MLR) and cells with stimulator activity co-purified with dendritic cells. Thus, these dendritic cells appear phenotypically and functionally similar to the dendritic cells that have been described in the mouse spleen and rat lymph node. The ability of the intestinal lymph cells to stimulate rat T cells was used to determine which of the two subsets of these cells were the prime responders in the rat MLR. These subsets, defined by monoclonal antibodies, have been shown by previous work to display close functional analogies to the Lyt 2+ and Lyt 2- subsets in the mouse and to the two human T-cell subsets that have been defined by monoclonal antibodies. It was found that the T-cell subset that contains the helper cells for antibody responses proliferated when irradiated, fully allogeneic or semi-allogeneic thoracic duct cells were used as stimulators, but the subset containing suppressor T cells did so only in the fully allogeneic system. Detailed studies showed that in the absence of helper cells in the responder population T cells in the stimulator population of helper phenotype were responsible for proliferation of the suppressor T-cell subset observed in fully allogeneic MLRs. Proliferation of the suppressor T-cell subset could be obtained using semi-allogeneic stimulators, provided that the F1 cells were derived from a source containing dendritic cells but it was shown that, as in the case with fully allogeneic stimulators, the helper T cells in the stimulator population were playing an active role. These results demonstrate that proliferation of the suppressor T-cell subset in the rat MLR is dependent on blastogenic activity provided by the helper T-cell subset and suggest that in some situations this blastogenic activity may arise through the recognition, by the helper cells, of environmental antigens presented on dendritic cells. It has been reported that in the human MLR both T-cell subsets proliferate but that only the helper subset does so when antigen-primed cells are stimulated with specific antigen. The present experiments, by emphasizing the activity of helper T cells in the stimulator population in the MLR, cast doubt on the implication that recognition of alloantigens in vitro differs in an essential way from that of soluble antigens.

Animals↗
PubMed1980

The kinetics of antibody binding to membrane antigens in solution and at the cell surface.

The reaction kinetics of 125I-labelled mouse monoclonal antibodies binding to three cell-surface antigens of rat thymocytes (Thy-1.1, W3/25) were studied. The differences between bivalent and univalent interactions were determined by using antibody in the F(ab')2 or Fab' form and by using antigen in polymeric or monomeric forms. Association rate constants (k+1), dissociation rate constants (k-1) and equilibrium constants were determined. Also, the dissociation kinetics of rabbit antibodies against rat Thy-1 antigen were studied. The major findings were as follows. (i) With F(ab')2 antibody there was no simple relationship between antigen density at the cell surface and extent of bivalent binding. Extensive univalent binding was observed unless the antibody had a high k-1 for the univalent interaction, in which case all binding was bivalent. (ii) k+1 values were similar for F(ab')2 or Fab' antibody, and for the different antibodies were in the range 0.8 x 10(5)--1.1 x 10(6) M-1.s-1. These differences were sufficient to affect the interpretation of serological assays with the different antibodies. (iii) Antibody bound bivalently dissociated much more slowly than that bound univalently. However, the k-1 values for the univalently bound antibody were sufficiently low in most cases that the lifetime of the univalent complex was similar to or greater than the time needed for the assay. Thus the results could be interpreted on the basis of irreversible reactions. The overall conclusion from the study is that for an understanding of the binding of antibody to cell-surface antigens the kinetics of the interaction are of major importance and theories based on equilibrium binding are inappropriate.

Animals↗