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Biomedical subjects

S C Knight

Publications and source records attributed to S C Knight.

At least 127 records · Page 7Linked to original sources
PubMed1987

Class II histocompatibility antigens on human dendritic cells.

Histocompatibility antigens of the HLA D locus on the surface of human dendritic cells (DC) were visualized in the electron microscope using immunogold labelling. DC from peripheral blood expressed DR that was frequently concentrated at junctions between aggregating DC and lymphocytes or DC and macrophages. Labelling with an antibody to DQ was more diffuse and was not concentrated at points of cell-cell contact. The D locus antibody RFD1 labelled DC in distinct patches that were sometimes located at points of cell contact. Upon labelling DC with antibody to DR and incubating the cells at 37 degrees, some label remained on the cell surface but some was found in deep channels which appeared to be formed between veils at the surface of the cell and became internalized in membrane-bound structures. Under the same conditions, gold bound to DQ molecules remained on the surface of DC. Gold labelling RFD1 also remained mainly on the cell surface but there was occasionally internalization of patches into the cells through depressions in the cell membrane. The changes in distribution of the label on warming the cells suggests that materials bound to different D locus products may be 'processed' differently.

Cell Adhesion↗
PubMed1986

Sensitivity of veiled (dendritic) cells to cyclosporine.

The effect of cyclosporine (CsA) on dendritic cell function was tested by pulsing rabbit veiled cells (VC, the "dendritic" cells from the afferent lymph) with the drug. This treatment inhibited their capacity to enhance proliferative responses of autologous peripheral blood lymphocytes to the mitogen concanavalin A. The concentration of CsA required to produce inhibition varied from one rabbit to another and ranged from 5 to 100 ng/ml. The degree of inhibition was greater under conditions in which the normal VC were more effective. Addition of further untreated VC restored the response, but this restoration was incomplete under some culture conditions. Pulsing peripheral blood mononuclear cells (PBM) with CsA also produced a reduction in the stimulation by Con A, and the response was not restored by addition of normal VC. The experiments did not distinguish whether the effect of CsA was directly on dendritic cell function or via a secondary effect of "presentation" of CsA to lymphocytes by the dendritic cells.

Animals↗
PubMed1986

The distribution of dendritic cells in the synovial fluids of patients with arthritis.

We have investigated the cellular composition of 108 consecutive samples of synovial fluid from patients with Juvenile Chronic Arthritis (JCA), Rheumatoid Arthritis (RA) and Osteoarthritis (OA). Particular emphasis was placed upon the enumeration of cells with dendritic morphology and the study of their in vitro function. Whilst the cellularity of the synovial fluids varied by a factor of greater than 100 within patient groups, the fluids obtained from patients with inflammatory arthritis (JCA & RA) were more cellular than those from patients with non-inflammatory arthritis (OA). This was also noted with respect to both the number and proportion of dendritic cells. The dendritic cells stimulated allogeneic mixed leucocyte reactions, and enhanced mitogenic responses of peripheral blood lymphocytes when present in numbers as low as 1% of the total mononuclear cells. Syngeneic stimulation of blood lymphocytes by similar numbers of dendritic cells was usually negative. However, occasionally there was a marked syngeneic stimulation, which may be evidence for the presentation of antigen by dendritic cells within the arthritic joint.

Arthritis↗
PubMed1986

Non-adherent, low-density cells from human peripheral blood contain dendritic cells and monocytes, both with veiled morphology.

Dendritic cells (DC) from human peripheral blood, known to adhere transiently and to become non-adherent by 16 hr, can be separated in the low-density interface on hypertonic Metrizamide gradients. Many more low-density cells (5.8% of the mononuclear cells separated on Ficoll) were obtained from the population that was non-adherent after only 90 min. Over 95% of these low-density cells had veiled morphology. A proportion were monocytes by phenotypic and phagocytic properties. One-third of the cells (on average) were DC on the basis of lack of monocyte phenotype and of potency as stimulators in the mixed lymphocyte reaction. Including both the 16 hr and 90 min non-adherent cells, over 2% of the mononuclear cells isolated from human peripheral blood may be DC.

5'-Nucleotidase↗
PubMed1986

Dendritic cells and the initiation of contact sensitivity to fluorescein isothiocyanate.

Lymph node cells taken 24 hr after skin-painting mice with the contact sensitizer fluorescein isothiocyanate (FITC) induce delayed-type hypersensitivity in recipient mice. Skin-painting increased the number of dendritic cells (DC) in the draining lymph nodes without significantly changing the number of lymphocytes at 24 hr. The antigen was preferentially located on the DC. Raising the dose of FITC increased both the number of DC and the amount per cell. The addition of these DC to syngeneic lymph node cells at a ratio as low as 1:300 initiated proliferative responses in vitro. The level of proliferation was related to the amount of antigen on the DC. Mice given 50,000 of these fluorescent DC developed specific contact sensitivity reactions. DC exposed in vitro to FITC also acquired antigen and were able to initiate proliferative responses in vitro and to sensitize recipient mice. The DC may therefore be the prime cell involved in the induction of delayed-type hypersensitivity.

Animals↗
PubMed1985

The role of dendritic cells in the initiation of immune responses to contact sensitizers. I. In vivo exposure to antigen.

Twenty-four hours after skin painting mice with picryl chloride (PIC) there was a four- to fivefold increase in the numbers of dendritic cells (DC) isolated from the lymph nodes. These DC initiated primary proliferative and cytotoxic responses when added to cultures of normal syngeneic lymph node cells. The proliferative response was enhanced when the donors of the responding lymph node cells were sensitized with the same antigen. Contact sensitivity developed in syngeneic mice injected into the footpads with 30,000-50,000 DC from lymph nodes of mice painted with picryl chloride 1 day previously. Thus, 1 day after skin painting mice, there were dendritic cells in the draining lymph nodes which were able both to initiate primary stimulation of lymphocytes in vitro and to sensitize recipient mice to give specific delayed hypersensitivity reactions.

Animals↗
PubMed1985

The role of dendritic cells in the initiation of immune responses to contact sensitizers. II. Studies in nude mice.

Twenty-four hours after skin painting nude mice with picryl chloride, there was an increase in the number of dendritic cells (DC) isolated from the draining lymph nodes. This increased inflow or retention of DC in lymph nodes following skin painting is therefore unlikely to depend on interaction of DC with T cells. The DC obtained initiated primary proliferative responses in vitro in lymph node cells from congenic euthymic mice. Contact sensitivity developed in congenic mice when they received footpad injections of 60,000 DC from the lymph nodes of nude mice skin sensitized 1 day previously with picryl chloride or oxazolone. The initiation of delayed hypersensitivity was therefore independent of T-cell contamination within the donor DC.

Animals↗
PubMed1985

In vitro stimulation of lymphocytes from patients with rheumatoid arthritis.

Peripheral blood lymphocytes from patients with rheumatoid arthritis (RA) and from normal controls were compared in 20 microliters droplet cultures following stimulation with phytohemagglutinin or concanavalin A. The dynamics of proliferation were significantly changed in RA. Higher numbers of cells in culture were needed to achieve the same response. This may explain the low proliferative responses of lymphocytes from some patients with RA, and apparent changes of in vitro suppressor effects, reported by other authors. Diurnal variations of lymphocytes in RA patients were also studied. No differences in the response to mitogen of lymphocytes taken at 7 AM and 7 PM were found.

Adult↗
PubMed1985

Influence of dendritic cells on tumor growth.

Dendritic cells (DC) exposed to antigen are potent initiators of immune responses, and the numbers of DC and the dose of antigen control the level of response. The influence of these variables was tested on the growth of mouse sarcoma cells in vivo. When normal syngeneic DC (100,000) were given to mice with palpable tumors, tumor regression or delay in tumor growth was obtained. DC exposed to increasing doses of tumor extract in vitro before administration had progressively less effect. DC exposed to antigen delayed tumor growth significantly only when given on the same day as 500 tumor cells. The studies suggested that low doses of antigen on DC elicit immune responses and that high doses block them. The numbers of antigen-presenting cells and the dose of antigen modulate the degree of immunity to mouse sarcoma in vivo.

Animals↗
PubMed1985

Defective low-density cells of dendritic morphology from the blood of patients with common variable hypogammaglobulinaemia: low immunoglobulin production on stimulation of normal B cells.

Low-density cells (LDC) of dendritic morphology from the blood of patients with common variable (late-onset) hypogammaglobulinaemia (CVH) did not induce allogeneic immunoglobulin production by normal B cells unlike LDC from normal blood. When LDC from patients were treated with pokeweed mitogen (PWM), a lower allogeneic secretion of IgM and IgG was induced in normal B cells than that induced by allogeneic normal LDC treated with PWM. B cells from hypogammaglobulinaemic patients were non-responsive to both normal and patient LDC treated with PWM under all conditions tested.

Agammaglobulinemia↗
PubMed1985

Suppression of collagen type II-induced arthritis by transfer of lymphoid cells from rats immunized with collagen.

Rats were immunized with type II collagen to induce polyarthritis. Spleen and lymph node cells were taken at various times and transferred to normal syngeneic animals. Disease was not observed in recipients of cells taken from donors either during the pre-clinical phase or the acute clinical phase of the disease. However, arthritis could not be induced in the recipient animals that had received cells taken from donors during the preclinical phase. Animals receiving cells from donors with clinical disease appeared to have a normal susceptibility to disease induced subsequently. In contrast with the differences in their susceptibility to induced disease, all recipient animals made unmodified antibody responses to a challenging injection of type II collagen. The results showed that before the appearance of clinical disease in CII immunized rats, there were cells in the spleen and lymph nodes that inhibit the development of disease but not antibody responses.

Animals↗
PubMed1984

Veiled cells--"dendritic cells" of the peripheral lymph.

The veiled cells (VC) of afferent lymph can be classified with dendritic cells (DC) of tissues on the basis of morphology, surface markers, cytochemical staining and function. VC form a population of cells, shown to carry antigens, in transit from the peripheral tissues to the paracortical areas of the lymph nodes. They can stimulate lymphocyte proliferation with antigens in vitro when added as less than 1% of the mononuclear cell population. They may initiate responses to foreign antigens such as keyhole limpet haemocyanin and 1-fluoro-2,4-dinitrobenzene (DNFB) and to alloantigen in the mixed leucocyte reaction or during grafting. VC may also be involved in antigen presentation in inflammatory and autoimmune diseases.

Animals↗
PubMed1984

Changes in the populations of lymphoid cells in human peripheral blood following physical exercise.

Marked lymphocytosis occurs after exercise. In a study of healthy volunteers this was dominated by one population lacking T cell and B cell determinants and another expressing the Leu 2a phenotype (cytotoxic/suppressor). Lymphocytes from two individuals were characterised further and a near five-fold increase in cells expressing antigens associated with natural killer (NK) cells (Leu 7 and Leu 11) was noted. In addition, these emergent lymphocytes, unlike most T cells, lacked acid alpha-naphthyl esterase activity. In functional studies, exercise led to significantly greater NK activity but, in spite of altering the distribution of lymphocyte subpopulations, there was no detectable change in the proliferative response to the T cell mitogen, concanavalin A, over a wide range of cell concentration, mitogen dose and time. The numbers of low density macrophages and dendritic cells increased concomitantly with the increase in total lymphocytes. We conclude that exercise increases the proportion of circulating NK cells and cells expressing the Leu 2a phenotype.

Cell Separation↗
PubMed1983

Induction of immune responses in vivo with small numbers of veiled (dendritic) cells.

The role of dendritic or veiled cells (VC) from lymph nodes or spleens of rats and mice in initiating immune responses in vivo has been investigated. Host-versus-graft responses were induced by injection of VC from spleens of (C57BL/10 X CBA) F1 mice into the footpads of parental strain (CBA) animals and measured by the increase in the weight of the draining popliteal lymph nodes. The potency of VC to induce the responses was 100-fold greater than that of unseparated spleen cells. The in vivo effect of VC was not limited to this direct allogeneic stimulation because autologous VC could also be used in the induction of an experimental autoimmune disease. In these studies, experimental allergic encephalomyelitis was produced in Lewis rats by injection of guinea pig brain and spinal cord material emulsified in Freund's complete adjuvant. Small numbers of VC from spleens or lymph nodes of rats showing clinical signs of experimental allergic encephalomyelitis induced a mild form of the disease when injected intravenously into normal Lewis rats. Thus, VC carrying antigen, either as an integral part of their surface membrane or acquired during exposure to antigenic substances, appeared to be very potent agents for the induction of immune responses.

Animals↗
PubMed1982

Double-blind controlled trial of immunosuppression in the treatment of multiple sclerosis: final report.

In a double-blind controlled trial 43 patients with relapsing-remitting multiple sclerosis were treated either with anti-lymphocyte globulin, prednisolone, and azathioprine, or with placebo preparations. Treatment began with a combination of the three medicaments but after 1 month was continued for another 14 months with azathioprine (3 mg/kg dialy) only. There was a marginally beneficial effect of immunosuppression on the overall relapse rate and clinical progression. However, there were significant effects on in-vitro lymphocyte function and in the visual evoked potentials in favour of the group receiving suppressive treatment. Placebo-treated patients of the HLA A3 tissue type had significantly more relapses than placebo-treated patients who were not of type HLA A3. Nevertheless, HLA-A3-positive patients treated with immunosuppression had significantly fewer relapses than A3-positive placebo-treated patients.

Adolescent↗