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Biomedical subjects

A Cooke

Publications and source records attributed to A Cooke.

At least 199 records · Page 11Linked to original sources

Antibody mediated regulation of immune responses. I. Enhancement of specific antibody responses through IgM antibodies.

Injection of monoclonal IgM antibodies to sheep red blood cells (SRBC) 2 h before immunization with a low dose of antigen (Ag) specifically enhances the direct and indirect plaque-forming cell response. This enhancement was specific: the specific antigen had to be present; the plaque-forming cell (PFC) response to TNP-Ficoll- or bromelein-treated mouse red blood cells was not enhanced; the PFC response to SRBC was not enhanced by injections of monoclonal antibody to TNP. The optimum conditions for enhancement were found to be dependent on both the dose and the time of administration of antibody in relation to antigen. The possible mechanisms for this enhanced antibody response are discussed.

Animals↗

Direct staining of mouse T lymphoblasts with fluoresceinated Vicia villosa lectin.

Fluorescein conjugated Vicia villosa (Vv) lectin was used for direct staining of the surface of viable cells of various mouse lymphocyte populations. A varying proportion of polyclonally-activated T cells expressed Vv receptor although less strongly than cells of an influenza virus-specific cytotoxic T lymphocyte (CTL) clone and blasts generated in the mixed lymphocyte reaction. Cyclosporin A (CyA) treatment markedly reduced the expression of Vv receptor following concanavalin A (Con A) stimulation by between 66% and 93% with a concurrent inhibition of blastogenesis and complete abrogation of cytolytic function. Resting mouse lymphocytes and B-cell blasts were always Vv-negative. However, non-specific suppressor factor producing non-cytotoxic T-cell lines also expressed Vv receptor as shown by the weak, but specific, surface fluorescence of EL4 and BW5147 cells stained with Vv. Vv-positive cells were not restricted to a particular Ly phenotype, Vv-positive cells being found among both Lyt 1+ and Lyt2+ MLC stimulated lymphocytes. Our data suggest that the receptor for Vv lectin cannot be regarded as an exclusive differential marker for CTL.

Animals↗

3H-collagen turnover in non-cross-linked and aldehyde-cross-linked dermal collagen grafts.

Using trypsin-purified rat dermal collagen labelled with tritiated hydroxyproline and proline, a study has been made of hydroxyproline turnover in non-cross-linked and glutaraldehyde- and formaldehyde-cross-linked collagen when implanted s.c. in unlabelled isogenic rats. Grafts cross-linked with 0.01% glutaraldehyde maintained their collagen mass over a 22-week period, loss of original collagen being balanced by the gain in new collagen (22% at 22 weeks). Cross-linking with 5% formaldehyde temporarily inhibited collagen loss as compared with non-cross-linked grafts. However, at 22 weeks both had lost some 30% of their collagen mass, the gain of new collagen (some 8%) only partially compensating for the loss of original implant collagen.

Animals↗

Apparent failure of thymic epithelium transplants to alter the course of autoimmune disease in NZB/W mice.

Thymic epithelium from neonatal DBA/2 mice (H-2d) was placed under the kidney capsule of 10- to 12-wk-old female NZB/W mice (H-2d/z). Donor epithelium, equivalent to 1-2 lobes of neonatal thymus, was either irradiated (1300 rad.) or cultured for 7 days in order to minimise host-versus-graft reactions. Histological examination showed that the epithelium repopulated and remained in place until the end of the experiment, with no sign of rejection. Despite this, the treated animals lived no longer than the untreated or sham operated controls. Levels of anti-nuclear antibody and serum IgM (normally highly elevated in these animals) were not significantly different in any group.

Animals↗

Hydroxyproline turnover in dermal collagen grafts in reconstituted skin wounds in the rat.

Using donor skin labelled with tritiated hydroxyproline and proline, a comparative study has been made of hydroxyproline (and by extrapolation collagen) turnover in skin, dermal collagen and glutaraldehyde crosslinked dermal collagen grafts in unlabelled isogenic recipient rats. In contrast with non-crosslinked collagen and skin grafts, collagen grafts stabilized by crosslinking with 0.01% glutaraldehyde underwent little loss of original graft collagen and maintained their original collagen mass over a 22 week period. As the skin grafts acquired a similar amount of new collagen to that lost, they also maintained their original mass. However, the non-crosslinked collagen grafts showed only a small gain of new collagen and lost 57% of their original mass.

Animals↗

Specific and non-specific suppressor cell activity in NZB mice.

Non-specific and specific suppressor cell activity has been examined in both young and old NZB mice and compared to normal CBA mice. Both young and old NZB mice are shown to be able to generate antigen non-specific and specific suppressor cells in response to Con A and rat RBC respectively. In addition, antigen-specific suppressor cells which suppress the experimental induction of red cell autoantibodies do not influence the spontaneous development or course of autoimmune haemolytic anaemia. Subsequent experiments showed that this is probably due to differences in specificity of induced and spontaneous autoantibodies.

Aging↗

Lack of autoantigen-specific splenic suppressor cells in mice with an X-linked B-lymphocyte defect.

Male and female progeny of a cross between CBA/N female and BALB/c male mice were tested for their ability to generate autoantigen-specific suppressor cells as a result of stimulation with crossreacting rat RBC. Male mice, hemizygous for the X-linked defect, were unable to generate these antigen-specific suppressor cells, whereas their female littermates behaved like the normal (CBA/Ca x BALB/c)F1 mice.

Animals↗

Sex differences in the regulation of experimentally induced autoantibodies in (NZB x NZW)F1 mice.

The ability to induce autoantibodies to erythrocytes in male and female (NZB x NZW)F1 mice was examined. Female (NZB x NZW)F1 mice were shown to produce significantly more autoantibody than the male (NZB x NZW)F1 mice. The regulation of this experimentaly induced autoantibody was studied by examining the ability of male and female (NZB x NZW)F1 mice to generate antigen-specific suppressor cells. A sex difference was found in the ability to generate these suppressor cells. Male mice generated antigen-specific suppressor cells in response to rat RBC which were capable to suppressing the experimental induction of red cell autoantibodies whereas female mice were unable to generate those antigen-specific suppressor cells.

Agglutinins↗

Effect of aldehyde cross-linking on human dermal collagen implants in the rat.

The fate of s.c. implants of fibrous, trypsin-purified human dermal collagen and collagen cross-linked with formaldehyde and glutaraldehyde has been studied in rats. Dermal collagen, and untreated skin implants, underwent resorption associated with a pronounced round-cell reaction. While collagen implants cross-linked with solutions of 0.04% and 0.08% formaldehyde became reduced in size, those cross-linked with 1% formaldehyde and 0.01%, 0.02% and 0.04% glutaraldehyde, although undergoing some collagen remodelling, retained their original size over the 25-week period of study. At 5 weeks the aldehyde cross-linked implants showed their greatest cellularity, reaching a lower, more stable cell population by 18 weeks. More round cells were seen at 5 weeks, particularly after formaldehyde cross-linking, than a later times when few were present. The results indicate that aldehyde-stabilized preparations of heterograft dermal collagen could have applications in the repair of tissue defects in man.

Aldehydes↗

Deficient production of anti-red cell autoantibodies by mice with an X-linked B lymphocyte defect.

The production of anti-self red cell antibodies has been studied in mice bearing the CBA/N X-linked B lymphocyte defect and their phenotypically normal littermates. Defective mice produced anti-self red blood cell (RBC) antibodies at markedly reduced levels after multiple injections of rat RBC. They also failed to show significant numbers of plaque-forming cells against enzyme-treated isologous RBC. These findings are discussed in terms of the nature of the CBA/N defect and the acquisition of a complete specificity repertoire.

Animals↗

Rabbit anti-EL4 serum. A reagent with specificity for a population of murine suppressor cells.

Antisera against the C57B1 (H-2b) mouse lymphoma, EL4 were prepared in rabbits. After absorption with mouse liver, red cells and thymocytes the antisera appeared to be cytotoxic for a subpopulation of peripheral T cells. The absorbed antisera blocked the immunosuppressor function of Con A-stimulated splenic lymphocytes, but was unreactive against Con A-stimulated and allogeneically primed cytotoxic cells, or helper T cells. Consequently, heteroantiserum against EL4 may provide a useful reagent for the differentiation of cytotoxic from suppressor T-cell subsets.

Animals↗