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Biomedical subjects

E Leuchars

Publications and source records attributed to E Leuchars.

16 recordsLinked to original sources
PubMed1979

Studies on hyperlymphoid mice.

Injection of syngeneic, but chromosomally distinguishable, lymph node or spleen cells into adult mice resulted in both T- and B-lymphocyte chimaerism. In spleen-injected mice haematopoietic chimaerism was also established. It appeared that the donor T lymphocytes were added to the host recirculating T-cell pool so that a hyperlymphoid state was produced. The percentage of donor T lymphocytes declined very slowly in normal mice, but remained stable in adult-thymectomized animals. There was no evidence of a homeostatic mechanism involving destruction of excess peripheral T lymphocytes or grossly affecting the flow of T lymphocytes from the thymus into the recirculating T-cell pool. A preliminary model of the T-lymphocyte system is proposed.

Animals↗
PubMed1979

Adult and pre-adult thymectomy of mice: contrasting effects on immune responsiveness, and on numbers of mitogen-responsive and Thy-1+ lymphocytes.

Peripheral lymphoid tissues of mice which have been thymectomized at 2 or 4 weeks of age, that is, before they achieve adult body weight, have been shown to be lacking in cells responsive to the T-cell mitogen, phytohaemagglutinin, when the animals became adult, and these mice have also been shown to have a deficient immune response against sheep erythrocytes. It is suggested these effects of pre-adult thymectomy are consequent upon removal of the prime source of T cells prior to the animal having acquired complete T-cell populations of the adult. Spleens and lymph nodes of mice thymectomized at 8 weeks of age were found to have reduced numbers of cells susceptible to the cytotoxic effects of anti-Thy-1 serum as early as 4 weeks after the operation, whereas the number of lymphocytes responsive to T-cell mitogens in these lymphoid tissues was not reduced at this time. The number of spleen-borne antibody-producing cells in a primary or secondary response was not affected by 8-week thymectomy, either when the response was tested in the operated animal, or after transfer of cells from such an animal to an irradiated recipient. The results are discussed with respect to other work on the effects of thymectomy of mice during the post-neonatal and pre-adult period.

Age Factors↗
PubMed1978

Studies of hyperthymic mice. I. The influence of multiple thymus grafts on the size of the peripheral T cell pool and immunological performance.

Following the implantation of syngeneic chromosomally marked thymuses under the kidney capsule of normal adult mice, donor T cells were found in the blood and other lymphoid organs. The mice were found to have increased numbers of Thy.1-positive cells in spleen and lymph nodes, increased peripheral blood lymphocyte levels and also augmented immune responses to sheep erythrocytes. The contribution made by an individual graft to the donor T cell pool was independent of the number of thymuses grafted as was the growth of the grafts themselves. The results reaffirm that there is no homeostatic feedback control of thymus growth in adult mice.

Animals↗
PubMed1978

Studies of hyperthymic mice. II. The influence of thymus grafts on cell flow through the peripheral T-cell pool.

In normal CBA/H mice implanted under the kidney capsule with eight CBA/H.T6T6 neonatal thymus lobes it was observed that the percentage of marked thymus-graft derived T cells in the periphery, after building up to a peak, showed a biphasic exponential decline. The initial decline was very rapid and appeared to be due to loss of the thymus-graft derived cells from the system. The later decline was slower and was the same as that of an introduced cohort of lymph-node lymphocytes. The second rate of decline was, however, considerably more rapid than that of lymph-node cohort in non thymus-grafted mice. We conclude that in multiply thymus-grafted mice the flow of cells through the T-cell pool is more rapid than in normal mice and that in this sense the thymus can be thought to drive the lymphoid system.

Animals↗
PubMed1978

The immunological response of CBA mice to P. yoelii. II. The passive transfer of immunity with serum and cells.

CBA mice infected with the malaria parasite Plasmodium berghei yoelii (P. yoelii) develop a self-resolving infection lasting 15-18 days; on recovery from a primary infection they are immune to further infection. Cell and serum transfers from immune to non-immune mice were used to analyse the mechanism of resistance. Whereas serum from mice which had recovered from a single infection was ineffective in transferring immunity, hyperimmune serum (from mice repeatedly challenged with P. yoelii) protected against challenge inocula of 10(4) and 5 X 10(4) but was ineffective against higher inocula (10(5)). Doses of serum which completely protected intact mice were ineffective when administered to T-cell deprived recipients. The injection of spleen cells from recovered mice conferred immunity on both normal and T cell deprived mice. Pretreatment of immune cell donors with cyclophosphamide reduce the ability of spleen cells to transfer immunity. Treatment of the immune cells with an anti-Thy 1 antiserum and complement in vitro did not abrogate their protective effect. The significance of these results is discussed in relation to the effector mechanisms which might operate in murine malaria.

Animals↗
PubMed1977

Effects of irradiation, anti-thymocyte serum and corticosteroids on PHA and LPS responsive cells of the mouse.

Peripheral lymphocytes responsive to stimulation by phytohaemagglutinin (PHA) and bacterial lipopolysaccharide (LPS) in culture have been quantitated following treatment of mice with anti-thymocyte serum (ATS), total body irradiation or corticosteroids. The ATS reduced the number of PHA-responsive cells in both blood and spleen, and induced splenomegaly, but it had little deleterious effect on spleen-borne LPS-responsive cells. In contrast, the spleens of mice treated with hydrocortisone acetate were atrophied and the remaining cells had a reduced LPS response and an enhanced PHA response. Total body irradiation impaired both PHA and LPS responsiveness in the spleen. Recovery of PHA responsiveness after either irradiation or ATS treatment was prolonged and was dependent on the presence of an intact thymus; recovery of LPS responsiveness after corticosteroid treatment was more rapid and was thymus-independent.

Animals↗
PubMed1977

The immunological response of CBA mice to P. yoelii. I. General characteristics, the effects of T-cell deprivation and reconstitution with thymus grafts.

Experimental infection of normal CBA mice with the parasite Plasmodium berghei yoelii (P. yoelii) resulted in a mild, non-fatal and self-limiting infection which lasted for 15-17 days. Animals which recovered from the primary infection were immune to reinfection though parasites could be detected in the kidneys of such mice 4 weeks after recovery from infection. (No plasmodia were demonstrated in the peripheral blood and other tissues examined.) In T cell-deprived mice, P. yoelii infections resulted in a progressive parasitaemia and proved fatal in 35-40 days. Studies of fluorescent antibody levels and morphological changes in the spleens of infected normal and T cell-deprived mice showed that while normal mice produced high levels of IgG1, IgG2 and IgM antiplasmodial antibodies and developed a strong and sustained germinal centre response, in T cell-deprived animals the production of IgG1 antibodies was almost completely abolished and the germinal centre response severely impaired. Reconstitution of T cell-deprived mice with syngeneic thymus grafts resulted in partial restoration of immunological responsiveness. P. yoelii infections in these reconstituted animals ran a self-limiting course akin to that seen in normal CBA mice; the level of protective immunity and the germinal centre response correlated with the degree of reconstitution achieved.

Animals↗
PubMed1976

The mitotic activity of, and antibody production by, sensitized lymphocytes quantified after transfer into irradiated recipients.

Adult thymectomized, irradiated CBA mice were reconstituted with bone marrow and thymus grafts derived from congenic strains differing in immunoglobulin allotype. After challenge with heterologous erythrocytes the allotype of the antibody secreted by the chimaeric spleen cells was the same as that of the bone marrow donor. When mixtures of immune and non-immune cells from the two congenic strains were transferred to irradiated recipients, a preponderance of the immune-donor cells was found dividing in the recipients' spleen 3 days after challenge with the immunizing antigen, and the allotype of the antibody-producing cells 7 days after challenge was almost entirely of immune-donor derivation. Further quantitative studies on the number of mitotically reactive cells observed after immunization with heterologous erythrocytes indicate that after primary and secondary challenge the mitotic activity of these cells is increased respectively four and eight times relative to that found in unsensitized cells.

Animals↗
PubMed1976

Thymus dependency of bone marrow stem cell proliferation in response to certain antigens.

The activity of mouse bone marrow CFU's following systemic injection of antigen has been investigated. In normal mice quiescent CFU's may be triggered into cycle after antigenic challenge. Prior adult thymectomy prevents stimulation of CFU if thymus-dependent antigens are injected but not when thymus-independent antigens or non-specific stimuli are used. Similar results were obtained in congenitally athymic mice. This seems to indicate an independent pathway for CFU triggering for each cell lineage and for T and B cells.

Animals↗
PubMed1975

On the sparse seeding of bone marrow and thymus in radiation chimaeras.

The repopulation of the thymus was studied in mice after a potentially lethal dose of irradiation and injection of different numbers of syngeneic but chromosomally distinguishable bone marrow cells. The more bone marrow cells were injected, the earlier was the changeover from dividing host cells to dividing donor cells observed. At both 30 and 60 days after irradiation, the number of donor-derived T cells in the peripheral blood responding to phytohemagglutinin was directly proportional to the number of donor bone marrow cells injected, but the number of host-derived T cells was inversely proportional. Experiments in which mistures of two syngeneic chromosomally distinguishable haematopoietic cell populations were injected after irradiation suggested that relatively small numbers of haematopoietic cells can be responsible for repopulating a single femur. Analysis of the thymus showed that the dividing cell populations within the thymus can also derive from very few precursor cells, possibly as few as one or two.

Animals↗
PubMed1975

The effect of Rauscher and Moloney leukaemia virus on amyloid development in casein-treated CBA mice.

Infection of adult CBA mice with Rauscher or Moloney leukaemia virus concomitantly with caseination significantly accelerated spleen amyloid development in irradiated, bone-marrow protected mice, but had no effect on untreated, adult thymectomized or thymectomized irradiated mice. Spleen tissue of mice infected with Moloney virus had the highest titre in the mice with accelerated amyloid development.

Amyloidosis↗