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B Seddon

Publications and source records attributed to B Seddon.

35 records · Page 2Linked to original sources
PubMed1996

CD4+CD8- thymocytes that express L-selectin protect rats from diabetes upon adoptive transfer.

Previous studies have shown that insulin-dependent diabetes can be induced in normal PVG.RT1u rats by a protocol of adult thymectomy and irradiation. The injection of CD4+ T cells from non-irradiated syngeneic donors prevents the onset of disease in approximately 50% of pre-diabetic recipients but all rats are protected if a particular subset of CD4+ cells is transferred. These protective cells express TCR alpha beta and have a memory phenotype, being CD45RClow RT6+. Further studies have demonstrated that the transfer of CD4+CD8- thymocytes, like that of unfractionated CD4+ peripheral T cells, also protects approximately half of recipients from diabetes suggesting that, as with the peripheral T cells, a functional heterogeneity may exist amongst CD4+CD8- thymocytes. In this study, we show that L-selectin is expressed by 50-60% of all CD4+CD8- thymocytes from 6-week-old rats. Adoptive transfer of these populations into thymectomized and irradiated rats revealed that the protection from diabetes observed by CD4+CD8- thymocytes was mediated almost entirely by the L-selectin+ subset. Cells with this phenotype were also able to mediate both humoral and cell mediated responses, providing primed B cells with help for secondary antibody responses and mediating local graft-versus-host reactions. L-selectin- CD4+CD8- thymocytes failed to mediate these responses. These data indicate that CD4+CD8- thymocytes must mature to the stage of L-selectin expression, before they can mediate normal T cell function. The implications of these results are discussed with respect to the possible role of murine NK1.1+ thymocytes in the control of autoimmunity.

Adoptive Transfer↗
PubMed1996

Effects of cytokines and glucocorticoids on endogenous class II MHC antigen expression by activated rat CD4+ T cells. Mature CD4+ CD8- thymocytes are phenotypically heterogeneous on activation.

By the use of mixed leukocyte cultures it was shown that a population of allogeneically activated rat T cells synthesize and express class II MHC antigens, in confirmation of other studies. Compatible with the finding that the MHC molecules detected on these cells were of T cell origin rather than passively acquired, it was found that mRNA for class II transactivator could readily be detected in the T cells stimulated in these cultures. In contrast there was no evidence that mouse T cells synthesized class II MHC antigens. The size of the population of activated rat T cells expressing class II MHC antigens was affected by the presence of IL-4 and glucocorticoids in the activating cultures. However, whereas IL-4 increased the frequency of thymocytes and peripheral T cells expressing class II antigens in culture, glucocorticoids diminished this frequency. The expression of class II MHC antigens by allogeneically activated thymocytes demonstrated a novel heterogeneity amongst mature CD4+ CD8- thymocytes that could not readily be accounted for in terms of differences in maturity of the cells, in the affinity of the TCR for the stimulating ligands or in the stage in the cell cycle. The data suggest that CD4+ single-positive thymocytes do not constitute a homogeneous population differing only in TCR clonotypes.

Animals↗
PubMed1995

The role of subsets of CD4+ T cells in autoimmunity.

It is generally considered that T cells which are reactive with self-antigens are effectively eliminated by two processes: clonal deletion and the induction of T cell anergy. More recently, it has been shown that some potentially autoreactive T cells remain unactivated because the self-antigens for which they are specific are not presented on competent antigen-presenting cells. All these mechanisms of self-tolerance may be regarded as passive in the sense that the autoreactive cells are either deleted or are intrinsically non-responsive. If this view of self-tolerance is adopted, then one would predict that rendering animals relatively lymphopoenic should not give rise to autoimmune disease. This prediction is not verified by experiment. Rats rendered relatively lymphopoenic by adult thymectomy followed by repeated low dose gamma-irradiation develop a high incidence of autoimmune diabetes. Furthermore, it has been shown that the reconstitution of these rats with a specific subset of CD4+ T cells from syngeneic donors prevents the development of this disease. The protective cells have the CD45RClow phenotype, they are resistant to adult thymectomy and the majority of them appear to be non-activated in the donor rats. In contrast, the CD45RChigh CD4+ subset does not provide protection from diabetes. Instead, on injection into athymic rats, it gives rise to pathological changes in a variety of organs: stomach, pancreas, liver, thyroid and lung. In addition, the CD45RClow CD4+ subset prevents these manifestations of autoimmunity in these circumstances. Recently, we have shown that CD4+ CD8- thymocytes are a highly potent source of cells that have the ability to control autoimmune diabetes in rats. It appears that the thymus has three distinct functions: positive selection; negative selection; and the generation of a population of cells that seem specialized for the control of autoimmunity.

Animals↗
PubMed1995

The relationship between ecophysiology, indigenous microflora and growth of Listeria monocytogenes in grass silage.

The combined effect of the physical and chemical parameters (oxygen tension, pH and dry matter) influencing Listeria monocytogenes growth and survival in silage were simultaneously studied in a model in vitro system. Ensiled grass was exposed to a range of low oxygen concentrations, 0-5% v/v, and their effect was recorded with respect to acidification and microbial population dynamics of the epiphytic microflora, i.e. lactic acid bacteria, enterobacteria, yeasts, moulds and L. monocytogenes in grasses pre-inoculated with the latter. Listeria monocytogenes survival depended on the establishment of a fine balance between the physico-chemical and microbiological characteristics, i.e. oxygen tension, dry matter, pH, grass and microbiological quality. In all grasses ensiled, an oxygen concentration of 1.0% or greater sustained L. monocytogenes growth, below this level growth was shown to be principally dependent on the rate and quality of the fermentation. In most grasses 0.5% oxygen prolonged survival, whereas 0.1% and 0% oxygen caused L. monocytogenes to die off. In very poor quality grass with a restricted fermentation L. monocytogenes survival was prolonged even under anaerobic conditions.

Anaerobiosis↗
PubMed1985

Effect of gramicidin S on the transcription system of the producer Bacillus brevis Nagano.

The effect of the peptide antibiotic gramicidin S, produced by Bacillus brevis Nagano, was tested on the transcription system of the producer by using in vivo, semi in vitro and in vitro systems for studies of RNA synthesis. The effects of other peptide antibiotics (linear gramicidin, tyrocidine and tyrothricin) were also tested for comparison. It was found that (a) RNA polymerase isolated from either gramicidin S-producing or non-producing strains had a similar structure and requirements and that (b) the presence of gramicidin S caused a very strong inhibition of the in vitro transcription system. We present evidence that this inhibition is most probably through formation of a complex between the antibiotic and the DNA. In vivo studies indicate that transcription during growth and sporulation is not affected by gramicidin S and the implication is made that gramicidin S inhibits transcription during germination and outgrowth.

Bacillus↗