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Biomedical subjects

S R Watson

Publications and source records attributed to S R Watson.

68 records · Page 4Linked to original sources
PubMed1980

Effect of chemotherapy on suppressor T cells in BCG-infected mice.

Specific pathogen-free B6D2 mice infected intravenously with 10(6) or 10(8) viable BCG Pasteur develop an anti-tuberculous immune response resulting in a progressive decline in viable BCG counts for the spleen and lung. Mice infected with 10(8) bacilli did not develop detectable levels of tuberculin hypersensitivity. Spleen cells harvested from both groups of mice at increasing time intervals after infection were T-cell enriched by nylon wool passage and tested for blast transformation following exposure to PHA or PPD. An early peak in tritiated thymidine uptake was observed following PPD exposure of cells from both the 10(6) and 10(8) groups. Cells from the latter group of animals developed a profound suppression to responsiveness to PPD throughout the remainder of the experiment. If the heavily infected mice were exposed to a regimen of 10 mg isoniazid plus 10 mg rifampin per 100 ml of drinking water for 30 days, the viable BCG population present within the lungs and spleen declined to near undetectable levels. This drop was associated with a decline in supressor T-cell activity demonstrated by appropriate cell-mixing experiments in vitro. The blastogenic responses to both PHA and PPD were substantially restored after 30 days of drug treatment. Treatment of the BCG infected mice within the first 7 days of infection prevented the development of the suppressor T-cell population.

Animals↗
PubMed1980

Development of suppressor T cells in mice heavily infected with mycobacteria.

Specific pathogen-free B6D2 mice were infected intravenously with 10(8) viable BCG, M. habana or M. simiae and the level of tuberculin hypersensitivity to 2.5 micrograms PPD or cytoplasmic protein antigens (CPA) prepared from the other organisms was determined using the footpad swelling test with increasing time after infection. This was correlated with the growth or persistence of mycobacterial populations within the liver. Spleen cells were removed from these infected mice and the level of blast transformation following exposure to PHA, PPD or M. habana or M. simiae CPA was measured in vitro. Early in the mycobacterial infections (day 14) thymidine incorporation by the spleen cells was significantly enchanced followed by a profound depression in incorporation rates as the infection progressed. The mechanism of this depressed response involved the production of suppressor T cells in the spleen. In the case of the M. simiae or M. habana infection, cells capable of mediating suppression were still present even after 12 months of infection. In the BCG infection, suppressor T cells declined with time so that by 4 months incorporation rates were back to normal and suppressor cells were no longer detectable in the spleens of the infected animals.

Animals↗
PubMed1979

Delayed hypersensitivity responses in mice and guinea pigs to Mycobacterium leprae, Mycobacterium vaccae, and Mycobacterium nonchromogenicum cytoplasmic proteins.

Antigenic relationships between Mycobacterium vaccae, M. nonchromogenicum, and M. leprae were examined in mice and guinea pigs injected with M. vaccae or M. nonchromogenicum suspensions. The growth of both organisms in outbred ICR and four inbred mouse strains was followed up to 30 days. M. nonchromogenicum persisted in the livers and spleens of the inbred mice substantially better than did the M. vaccae population in the same mouse strains. A translucent colony variant of M. vaccae isolated from the opossum survived in vivo better than the opaque colony isolated from opossums and cattle. Persistence of M. vaccae and M. nonchromogenicum was not markedly increased in T-cell-depleted (nude) mice. Normal mice infected with increasing numbers of M. vaccae did not develop delayed-type hypersensitivity to the homologous M. vaccae cytoplasmic protein antigen. When heat-killed M. vaccae were incorporated into Freund adjuvant, both mice and guinea pigs developed delayed hypersensitivity to cytoplasmic antigens prepared from M. vaccae, M. nonchromogenicum and M. vaccae vaccines cross-sensitized guinea pigs to the M. leprae cytoplasmic antigens.

Animals↗
PubMed1979

Suppressor T-cells in BCG-infected mice.

Specific pathogen-free B6D2 hybrid mice were infected with high (10(8) cells, intravenous), moderate (10(6) cells, intravenous), and low 10(3) cells, aerogenic) doses of viable BCG Pasteur. The growth of the BCG in the lungs and spleens of the three groups was followed over a 90-day period and correlated with the level of tuberculin hypersensitivity. Spleen cells were harvested from the three groups of mice at increasing time intervals and filtered through nylon wool to remove adherent cells, and the level of blast transformation after exposure to phytohemagglutinin and purified protein derivative was determined. Early in the BCG infection both the high- and the intermediate-dose groups showed enhanced thymidine incorporation by the spleen cell cultures, followed by a profound depression late in the infection. At this time, both groups of mice were anergic to purified protein derivative injected into footpads. Cell mixing studies demonstrated the presence of a population of suppressor cells in the spleens of the anergic animals. The suppressive abilities of these cells would be ablated by treatment with anti-Thy-1 antiserum and complement. The aerogenically infected mice were unresponsive to purified protein derivative but showed no evidence of suppressor T-cells. The lack of tuberculin sensitivity in these mice seemed to be due to a lack of sensitized T-cells in the spleen rather than to active immunosuppression.

Animals↗
PubMed1979

Development of suppressor T-cells in Mycobacterium habana-infected mice.

Mice were infected intravenously with increasing numbers of Mycobacterium habana (simiae serotype II), and the levels of delayed-type hypersensitivity to purified protein derivative and M. habana cytoplasmic protein antigen were determined after 14, 30, and 90 days. A footpad delayed-type hypersensitivity response was seen in 14-day-infected mice and was followed by a persisting anergy. T-cell-enriched suspensions collected 30 and 90 days into the infection (anergic donors) showed depressed transformation indexes after phytohemagglutinin and M. habana cytoplasmic protein antigen treatment in vitro. The corresponding B-cell mitogen (lipopolysaccharide) responses were not affected. Mixing experiments with T-cell-enriched suspensions from day-90 M. habana-infected donors adoptively suppressed lymphocyte transformation by normal and day-14 spleen cells. This effect could be ablated by anti-theta serum and complement treatment of the day-90 cells, indicating that the lack of in vitro responsiveness to cytoplasmic protein antigen was mediated by a population of suppressor T-cells present in the heavily infected spleens. There was no evidence that similar cells were present in the spleens of the 14-day-infected animals. Suppressor T-cells could be induced in vitro by exposure of day-14 spleen cells to concanavalin A or M. habana cytoplasmic protein antigen before they were mixed with normal or day-14 indicator splenic lymphocytes. The timing of the appearance of suppressor T-cells in the infected spleens corresponded to a loss of footpad hypersensitivity by the M. habana-infected animals.

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PubMed1977

The adjuvant effect of Corynebacterium parvum: T-cell dependence of macrophage activation.

Splenic and peritoneal macrophages from mice treated with Corynebacterium parvum enhanced the antibody response in vitro of normal nonadherent spleen cells to SRBC, but not to DNP-POL. This enhancement was dependent on the dose and time of administration of C. parvum and could be abrogated by pretreatment with carrageenan. Macrophages from T-cell-depleted mice failed to enhance the response, but this ability was restored if the mice had been reconstituted with purified T lymphocytes. Macrophages that are activated by C. parvum are a resident nondividing population. It is postulated that activated macrophages, capable of enhancing antibody responses to T-cell-dependent antigens, arise through a cell-mediated reaction to C. parvum.

Adjuvants, Immunologic↗
PubMed1977

Antibody response in vitro of spleen cells from Plasmodium yoelii-infected mice.

The primary antibody response to sheep erythrocytes and dinitrophenylated Ficoll of spleen cells from mice infected with Plasmodium yoelii was studied in vitro. The response to sheep erythrocytes was enhanced between 2 and 4 days after infection and depressed at later intervals. Cell fractionation experiments carried out at the time of immunosuppression indicated a defect of macrophage function. At the same time the response to dinitrophenylated Ficoll was normal.

Animals↗
PubMed1977

Enhancement of the antibody response in vitro by adherent cells from mice infected with Mycobacterium lepraemurium.

Spleen cells from mice systemically infected 4 to 6 weeks previously with Mycobacterium lepraemurium gave an enhanced primary antibody response in vitro to sheep erythrocytes, but responded normally to dinitrophenylated polyumerized flagellin. The ability to enhance the response was associated with the glass-adherent spleen cell population and with peritoneal cells. Similar cells obtained from infected mice depleted of T lymphocytes failed to enhance the antibody response. These studies suggest that macrophages that became activated during the development of cell-mediated immunity to infection can also stimulate antibody responses to thymus-dependent antigens.

Animals↗
PubMed1977

A re-evaluation of the role of macrophages in carrageenan-induced immunosuppression.

Administration of a single dose of 1 mg carrageenan to mice cause a temporary blockade of hepatic phagocytosis of 51Cr-labelled sheep erythrocytes (SRBC) and a prolonged reduction in the number of splenic plaque-forming cells (PFC) against SRBC. The in vitro responses to phytohaemagglutinin (PHA) and SRBC were also suppressed, whereas the response to the T cell-independent antigen DNP-Ficoll was not affected. Other in vitro experiments have shown that responses of normal cells can be actively suppressed by macrophages from carrageenan-treated mice and the possible mechanisms of this suppression are discussed.

Animals↗
PubMed1976

The role of macrophages in the adjuvant effect on antibody production of Corynebacterium parvum.

Spleen cells from mice pre-treated with C. parvum gave an enhanced in vitro antibody response to SRBC, but not to DNP-POL. This enhancing activity was associated with the adherent, but not the non-adherent spleen cell population and was found to be radioresistant. It is concluded that macrophages are directly involved in the adjuvant effect of C. parvum and the possible mechanisms of action are discussed.

Adjuvants, Immunologic↗
PubMed1976

Mouse T-cell tumour immunoglobulin. I. Antigenic properties and effects on T-cell responses.

The mouse T-cell tumours E1-4 and WEHI-22 produce an immunoglobulin (TCT Ig) which suppresses the antibody response to T- dependent antigens in vitro while having no effect on responses to T-independent antigens. TCT Ig also augments IgG responses to both kinds of antigen. TCT Ig appears to be a new class of mouse Ig because its effects on in vitro antibody responses can be absorbed by antisera to mouse Kappa chains but not with antisera to any of the known classes of mouse Ig. Furthermore, TCT Ig activity cannot be duplicated by free light chains, Fab2 fragments, several mouse serum Ig preparations of Ig made from B cells. TCT Ig affects only T-cell function in antibody responses. It has no effect on the ability of the different subclasses of T cells to respond to mitogens or to alloantigens. Furthermore, it does not block T-T cell co-operation suggesting that the molecular basis for T-T co-operation differs from that of T-B co-operation.

Animals↗
PubMedDate not supplied

Immune responses to atypical mycobacterial lung infections.

Various species of atypical mycobacteria exhibited a wide range of growth patterns in the lung, liver, and spleen of specific pathogen-free B6D2 mice infected with these organisms. The growth varied from rapid elimination (complete avirulence) to a continued persistence in the lung, which eventually resulted in the death of many of the mice. Prior depletion of the T cells of aerogenically challenged mice did not affect the growth characteristics of the organisms within the lungs. Mice infected with Mycobacterium habana developed an early hypersensitivity response to the cytoplasmic protein antigens (CPA) of this organism, and this response was followed by a persistent state of anergy. Mice infected with Mycobacterium simiae failed to develop detectable levels of hypersensitivity at any time during the study. Spleen cells taken from mice infected with M. habana or M. simiae exhibited an early peak in the incorporation of [3H] thymidine after exposure of the cells to the nonspecific T-cell mitogen phytohemagglutinin (PHA). A similar peak occurred when the cells were exposed to the specific mitogen CPA of M. habana. Later in the infection, the anergic spleen cells showed no transformation of lymphocytes after exposure to either PHA or CPA. T-cell-mixing experiments, which were carried out both before and after treatment of suspensions of cells from the anergic spleens with anti-Thy 1.2 antiserum plus complement, indicated the presence of a population of suppressor T cells in the anergic animals.

Animals↗
PubMedDate not supplied

Further studies on the enhancement of the antibody response in vitro by C. parvum.

We have shown previously that spleen cells from mice pre-treated with C. parvum give enhanced antibody response when cultured in the presence of thymus-dependent antigens. In order to establish if C. parvum has a similar effect when added in vitro, spleen cells from untreated mice were cultured with C. parvum in Marbrook chambers with sheep erythrocytes (SRBC) as antigen. At concentrations of 35-140 microgram/ml/20 x 10(6) spleen cells C. parvum enhanced, but at higher concentrations suppressed the in vitro response. Cultures containing lymphocytes from C. parvum treated mice and adherent cells from untreated animals, which do not show in vitro the enhancement in the absence of C. parvum, gave higher responses to SRBC when a critical dose of the vaccine was added. Supernatants from cultures of normal spleen cells with added C. parvum could enhance the in vitro response of normal spleen cells. In double Marbrook cultures, cells from mice pre-treated with C. parvum and cultured with this organism failed, however, to enhance the response of untreated cells in the outer vessel. Under these conditions the response was enhanced only when SRBC were also present in the inner vessel.

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