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P Garside

Publications and source records attributed to P Garside.

53 records · Page 3Linked to original sources
PubMed1995

CD4+ but not CD8+ T cells are required for the induction of oral tolerance.

It has been suggested that oral tolerance is mediated by CD8+ T lymphocytes, but the functional properties of these cells are unclear. Here we show that the induction of tolerance by feeding mice ovalbumin (OVA) does not prime antigen-specific class I MHC-restricted cytotoxic T cells in vivo. Indeed, such responses are markedly suppressed in mice fed OVA, and the induction of oral tolerance is abolished by depletion in vivo of CD4+ but not CD8+ T cells. These results indicate that CD8+ lymphocytes are unlikely to play a major role in the induction of oral tolerance and are the first demonstration that specific cytotoxic responses to an exogenous antigen can be suppressed by feeding antigen.

Administration, Oral↗
PubMed1994

Merger mania.

Explore the source record for details and available documents.

Communication↗
PubMed1994

Regulation of the immune response by nitric oxide differentially produced by T helper type 1 and T helper type 2 cells.

The balance between T helper type 1 (Th 1) and T helper type 2 (Th2) cells determines the outcome of many important diseases. Using cloned murine T cell lines, evidence is provided that Th1, but not Th2, cells can be activated by specific antigens or a T cell mitogen, concanavalin A, to produce large amounts of nitric oxide (NO). Furthermore, NO can inhibit the secretion of interleukin (IL)-2 and interferon-gamma by Th1 cells but has no effect on IL-4 production by Th2 cells. Th1 and Th2 cells can, thus, be distinguished by their differential production of and susceptibility to NO. NO exerts a self-regulatory effect on Th1 cells which are implicated in immunopathology.

Animals↗
PubMed1994

Differential cytokine production associated with distinct phases of murine graft-versus-host reaction.

Previous studies which demonstrated that cytokines such as interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) are essential for the development of graft-versus-host reaction (GvHR) did not establish whether the individual cytokines were responsible for distinct features of the disease. In this report, we show that IFN-gamma production is associated with the early proliferative phase of the disease, whereas the late, destructive phase correlates with production of TNF-alpha. These studies may assist in the development of specific immunotherapies aimed at individual aspects of immunologically mediated disease.

Animals↗
PubMed1993

Sensitivity to ivermectin and pyrantel of Ancylostoma ceylanicum and Necator americanus.

Experiments were carried out in the hamster to compare the relative susceptibility of Necator americanus and Ancylostoma ceylanicum to treatment with ivermectin. A. ceylanicum was found to be 300 times more sensitive to the anthelmintic with a 50% effective dose (ED50) of the order of 10-15 micrograms kg-1 body weight whilst that for N. americanus approximated to 3-5 mg kg-1. Furthermore, whereas complete clearance of A. ceylanicum was observed with a dose of 100 micrograms kg-1, N. americanus was not totally removed after treatment with 25 mg kg-1, the highest dose tested. Both parasites proved equally sensitive to pyrantel with an ED50 of 1-12 mg kg-1 for A. ceylanicum and 5-25 mg kg-1 for N. americanus. Treatment with pyrantel at 100 mg kg-1 completely eliminated worms of both species and doses of 25-50 mg kg-1 were > 90% effective. In addition to worm burdens, changes in host weight and PCV were also recorded and it was shown that both parameters could be used to evaluate the success/failure of treatment.

Ancylostoma↗
PubMed1993

Analysis of enteropathy induced by tumour necrosis factor alpha.

Tumour necrosis factor (TNF)-alpha has been implicated in the pathogenesis of experimental and clinical enteropathy, but its exact role is unknown. We show here that a single dose of TNF-alpha causes significant small intestinal pathology in normal adult mice, which develops within 15 minutes, persists for up to 48 hours and is enhanced by interferon-gamma (IFN-gamma). The enteropathy consists of villus atrophy and crypt hyperplasia and is therefore similar to that found in immunologically mediated enteropathies such as graft-versus-host reaction (GvHR). TNF-alpha is also cytotoxic to an intestinal crypt cell line in vitro. Thus, a direct action of TNF-alpha on crypt cells may be involved in its enteropathic effects in vivo. Together, these findings indicate that TNF-alpha alone, or in concert with other cytokines, may be an important effector molecule in immunologically mediated intestinal pathology and may ultimately provide a target for specific immunotherapy for clinical enteropathies.

Animals↗
PubMed1993

Is tumour necrosis factor alpha the molecular basis of concomitant immunity in schistosomiasis?

Prior to the development of high levels of resistance to infection with schistosomes, some mechanism appears to limit the number of productive worms in individuals, since children do not become superinfected, despite continued exposure to infection. One way in which infection levels might be limited, is through the generation of a concomitant immunity. Concomitant immunity results in the destruction of newly invading schistosomula whilst established adult worms continue to survive. Recent studies have provided evidence that TNF alpha enhances worm fecundity and is essential for granuloma formation. TNF alpha may therefore be important in worm reproduction and transmission, since the granuloma may serve to assist the passage of the eggs out of the tissues. With the additional evidence that the cytotoxic activity of lymphokine-activated macrophages against schistosomula may be, at least in part, due to the action of TNF alpha, we propose that TNF alpha may also be responsible for the phenomenon of concomitant immunity.

Animals↗
PubMed1993

A role for interleukin-1 alpha in immunologically mediated intestinal pathology.

Interleukin-1 (IL-1) is an important mediator of inflammation and has been implicated in several forms of immunopathology. Here we have investigated whether IL-1 plays a role in the enteropathy which occurs during a graft-versus-host reaction (GVHR) in mice. Non-irradiated (CBA x BALB/c) F1 mice with GVHR had increased production of IL-1 and treatment with rabbit anti-IL-1 alpha antibodies abolished the crypt hyperplasia and significantly reduced the parallel increase in crypt length which occurs in the jejunum. Antibody treatment had no effect on the accompanying increase in intraepithelial lymphocyte (IEL) counts or on the splenomegaly. Recombinant IL-1 itself produced villus atrophy, crypt hyperplasia and increased IEL counts in normal mice and stimulated the proliferation of an intestinal epithelial cell line in vitro. We propose that IL-1 plays an effector role in immunologically mediated enteropathy, either via direct effects on epithelial cells or secondary to an action on other, stromal cells in the mucosa.

Animals↗
PubMed1993

Natural killer cells and tumour necrosis factor-alpha-mediated enteropathy in mice.

We have shown previously that normal mice given interferon-alpha/beta (IFN-alpha/beta) or tumour necrosis factor-alpha (TNF-alpha) develop marked intestinal pathology which is similar to that found in enteropathies associated with cell-mediated immunity in vivo, such as graft-versus-host reaction (GVHR). The enteropathy induced by IFN-alpha/beta and GVHR are both dependent on the presence of natural killer (NK) cells and here we have examined whether NK cells are also required for enteropathy caused by TNF-alpha. Mice injected with recombinant TNF-alpha displayed enhanced splenic NK cell activity and developed significant villus atrophy and crypt hypertrophy in the small intestine. Administration of anti-asialo GM1 antibody abolished the NK cell activity in both normal and TNF-alpha-injected mice, but had no effect on the enteropathy caused by TNF-alpha. We conclude that NK cells are not required for TNF-alpha to damage the small intestine.

Animals↗
PubMed1992

Nitric oxide mediates intestinal pathology in graft-vs.-host disease.

We have investigated the involvement of nitric oxide (NO) in intestinal graft-vs.-host reaction (GvHR) in mice. Treatment of mice with L-NG-monomethyl arginine (L-NMMA), a specific inhibitor of NO synthesis, abolished the mucosal pathology of intestinal GvHR and reduced the associated lymphocytic infiltration of the epithelium. L-NMMA had no effect on splenomegaly in GvHR, nor did it interfere with the growth of an undifferentiated crypt stem cell line, or the production of tumor necrosis factor-alpha by activated macrophages in vitro. In contrast, L-NMMA inhibited the enhanced activity of natural killer (NK) cells which occurs in GvHR. We conclude that a NO-dependent mechanism is essential for intestinal immunopathology in GvHR and that this may reflect a role for NO in NK cell function.

Animals↗
PubMed1992

T lymphocyte dependent enteropathy in murine Trichinella spiralis infection.

Mice infected with Trichinella spiralis developed significant enteropathy, comprising villus atrophy, crypt hyperplasia, goblet cell hyperplasia and a decrease in intra-epithelial lymphocyte numbers by 10 days post-infection, when most of the parasites had been expelled from the gut. However, worm expulsion was prevented by treatment with cyclosporin A and, despite a continued parasite burden, cyclosporin A treated animals had no villus atrophy or changes in inflammatory cell numbers. These results confirm that the expulsion of T. spiralis from the mouse gut is accompanied by a significant intestinal lesion and that both of these phenomena are T-cell mediated.

Animals↗
PubMed1991

The role of interferon alpha/beta in the induction of intestinal pathology in mice.

We have investigated the role of interferon-alpha/beta (IFN-alpha/beta) and IFN-dependent effector cells in causing enteropathy in mice. The IFN-inducer polyinosinic:polycytydylic acid (poly I:C) augmented the natural killer (NK) cell activation normally seen in neonatal (CBA x BALB/c)F1 mice with graft-versus-host reaction (GVHR) and exacerbated the systemic and intestinal consequences of GVHR. Poly I:C itself produced a similar pattern of intestinal pathology when administered to normal mice. The effects of poly I:C on NK cell activity and intestinal architecture in normal mice could be reproduced by a single injection of purified IFN-alpha/beta and the intestinal lesions caused by IFN-alpha/beta were prevented by in vivo depletion of NK cells with anti-asialo GM1. These results indicate that IFN-alpha/beta may play an important role in immunologically mediated enteropathies by virtue of its ability to activate NK cells.

Animals↗
PubMed1990

Acquired immunity to Ancylostoma ceylanicum in hamsters.

A laboratory model of acquired immunity to human hookworm is described. Significant resistance to challenge infection with Ancylostoma ceylanicum was elicited in mature DSN hamsters. The serum and mucosal antibody responses were investigated in both quantitative and qualitative terms and changes associated with immunity were identified. Marked differences in numbers of mast and goblet cells in the small intestine were also recorded and related to the immune status of the host.

Ancylostoma↗
PubMed1989

The immune response of male DSN hamsters to a primary infection with Ancylostoma ceylanicum.

The immune response of hamsters to a chronic hookworm infection has been investigated. Ancylostoma ceylanicum caused long term infections in hamsters which were associated with prominent changes in secondary lymphoid organs. The mesenteric lymph nodes and spleens increased rapidly in size stabilizing at approximately 3-4 times the weight in control animals by weeks 3-7. Cells from both the mesenteric lymph node and spleen, after an initial period of increased blast cell activity, became less reactive in the latter stages of infection. Serum antibody responses were marked, commencing in weeks 3-4 and increasing in intensity throughout the 10 week period of measurement. The results are discussed in relation to their contribution to the understanding of human hookworm infection.

Ancylostoma↗
PubMed1989

Ancylostoma ceylanicum in the hamster: observations on the host-parasite relationship during primary infection.

The course of primary infection with a hamster-adapted strain of Ancylostoma ceylanicum was studied in inbred DSN and randomly bred WO/GD and WO/CR hamsters. Infective larvae were administered orally and began to develop in the small intestine without embarking on a tissue migration. Only the occasional larva was detected in other organ sites. It was concluded that the developing larvae moulted on days 3-4 and again to the pre-adult stage about 9-11 days post-infection. Worm burdens in infected hamsters were stable for at least 11 weeks after infection. There was no sudden expulsive phase and some adult worms survived for over 200 days. Overall the sex ratio of worms in groups of hamsters killed concurrently was about 50% although occasionally the ratio was biased in favour of one sex in individual animals. The blood packed cell volume (PCV) was significantly depressed 2 weeks following infection and continued to decline until a point of stability was achieved 4-5 weeks post-infection. The PCV subsequently remained depressed throughout the period of observation. Infected hamsters lost weight if kept in groups, but not when housed in separate cages. Groups of animals which lost weight did not recover to normal values within 11 weeks of infection. It is suggested that this model of hookworm infection has scope for exploring aspects of the host-parasite relationship which the canine models cannot fulfill adequately.

Ancylostoma↗