Development of immunosuppressor cells. Exertion of specific suppression by neonatal liver cells.
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Animals↗
Biomedical subjects
N Trainin
Publications and source records attributed to N Trainin.
Severe disseminated adenovirus infection successfully treated with a thymic humoral factor, THF.
Adenovirus and other usually benign viral infections may occasionally be associated with severe fulminant disease, often accompanied by acute acquired cellular immunodeficiency. Thymic humoral factor derived from calf thymuses has been demonstrated to have the capacity to restore the immunocompetence of immature, incompetent T cells. This factor was used in the treatment of a 3 1/2-year-old boy who was critically ill with an adenovirus infection and presented evidence of immunocellular deficiency. Within less than 48 hours after the institution of treatment with thymic humoral factor there was a dramatic, progressive clinical improvement, with restoration of the cellular immunocompetence. It is suggested that thymic humoral factor may be beneficial in the treatment of severe viral infections associated with depressed cellular immunocompetence.
Adenoviridae Infections↗
Immune deficiency of T system with possible T cell regulatory activity defect.
The occurrence of T system immunodeficiency in an infant together with excessive production of IgM and, to a lesser degree, of IgG and IgA, is an unusual combination. A case is reported in which an unremitting lung infection with lymphadenopathy and hepatosplenomegaly developed in a previously healthy two-month-old infant. Leukocytosis with lymphocytosis, monocytosis and eosinophilia was rapidly followed by leukopenia and lymphocytepenia after a blood transfusion for anemia. There was a transient clinical remission, but on relapse 10 days later, quantitative and functional T cell deficiency was found together with increased IgG and IgA and with IgM values reaching 50 times greater than normal. Thymic humoral factor was successful in vitro in increasing the number of identifiable T cells (E rosetts) as well as T cell function (leukocyte migration inhibition factor production). However, the infant died suddenly, and at autopsy evidence of a generalized inflammatory reaction compatible with a viral infection was found. The thymus was small, hypoplastic and hypocellular. It is speculated that the T system deficiency may have been acquired following Epstein-Barr virus infection, and that T cell regulatory activity of immunoglobulin production was defective.
Antibodies, Viral↗
Effect of thymic humoral factor on intracellular levels of cyclic AMP in human peripheral blood lymphocytes.
The exposure of human peripheral blood lymphocytes to thymus hormone causes an increase in the intracellular cyclic AMP level in these cells. Studies of the thymus-hormone-induced changes in cellular cyclic AMP levels revealed that cord blood lymphocytes contain significantly more target cells for the hormone than adult peripheral blood lymphocytes. The data obtained also suggest that the interaction between the hormone and its target cell is not readily reversible and that only a certain proportion of target cells in a given population of lymphocytes can be activated by a constant and limited amount of thymus humoral factor.
Adult↗
Thymic hormone (THF) therapy in immunosuppressed children with lymphoproliferative neoplasia and generalized varicella.
Four children with lymphoproliferative malignant disease, two with acute lymphocytic leukemia in remission and two with Hodgkin's disease, were treated with a Thymic Hormone, THF, for disseminated varicella infecition. It is suggested that THF increased significantly the number of peripheral blood lymphocytes and T-rosette forming lymphocytes in 3 out of 4 children, who developed the varicella at the time of impaired cellular immunity. On the other hand, in the fourth child, with Hodgkin's disease, who had a normal number of T-rosettes, a decreased absolute number of lymphocytes as well as T-rosettes was observed over a course of 14 days THF treatment, although the percent of T-cells has not changed significantly. All of the four children recovered, including the child who was at high risk, with a marked lymphopenia, severe bilateral pneumonitis, hepatitis secondary infected skin lesions and psudomonas sepsis. It is indicated that THF therapy may restore the depressed cellular immunity in immunosuppressed children with malignant disease, and has its value as a supportive immunotherapy in life-threatening disseminated varicella infection.
Chickenpox↗
Effect of thymic hormone on the response of different lymphoid cell populations to T mitogens.
The effect of the thymus humoral factor (THF) on the response of different lymphoid cell populations to T mitogens was studied. Lower THF concentrations were required to increase the response to concanavalin A (Con A) than to increase that to phytohemagglutinin (PHA), suggesting that T cell types at various stages of maturation are activated at different THF concentrations. Lower THF concentrations were required to enhance the mitogenic response of thymus cells than to enhance the mitogenic response of spleen cells, and this may be because of the higher incidence of target cells for THF activity in the thymus cell population. Spleen cells of adult thymectomized mice exhibited a higher sensitivity for THF than cells of intact control mice. Lymph node cells showed no increase in motogenic response after THF treatment. Similarly, THF did not affect the mitogenic response of spleen cells from nude mice. These results confirm our hypothesis that the targets for THF activity are the younger cells within the T cell lineage.
Animals↗
Kinetics of the response of spleen cells from tumor-bearing animals in an in vivo tumor neutralization assay.
The behavior of spleen cells from tumor-bearing mice, vis-à-vis isologous tumor cells, was investigated by means of an in vivo adoptive neutralization test. C3H/eB mice were challenged with tumor cells from a chemically induced fibrosarcoma. Spleens from these animals were removed at weekly intervals following tumor inoculation, mixed with tumor cells, and tested for their influence on tumor growth in syngeneic recipient mice. Two phases in the reactivity of spleen cells from tumor-bearing mice were clearly distinguishable. In a first stage of tumor growth, these mice yielded specific tumor-inhibitory cells conferring protection. Subsequently, the protective activity declined leading to a second phase characterized by tumor enhancement. Both protective and enhancing activities were shown to be mainly dependent on the presence of T cells.
Animals↗
Control of autoimmune processes by a thymic humoral factor (THF).
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Animals↗
Isolation and partial chemical characterization of THF, a thymus hormone involved in immune maturation of lymphoid cells.
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Amino Acids↗
Depletion of suppressor T cells in syngeneic chimeric mice.
The present results suggest that some T-cell activities of syngeneic chimeric mice such as T-cells involved in the antibody response to SRBC and MLC reaction are intact. On the other hand, suppressor T-cells involved in the regulation of the immune response to PVP and enhancement of 3LL tumor growth, and cells mediating CML reaction are damaged.
Animals↗
Augmentation of cell mediated lysis (CML) by THF.
The in-vitro model of cell mediated lysis (CML) was used to study whether a thymic hormone (THF) participates in the processes which lead to generation of effector cells. It was found that THF increases the capacity of effector cells from spleens of intact mice in the CML assay. This effect of THF on generation of effector cells was manifested when THF was present during the mixed lymphocyte culture. On the other hand, addition of THF to the effector (CML) phase did not elevate the lytic capacity of killer cells. Moreover, THF compensated the impaired lytic capacity of effector cells from adult thymectomized mice and raised it to the level of intact mice. The results are compatible with the hypothesis that THF acts on the generation of CML effector cells of both intact and adult thymectomized mice.
Animals↗
The role of the thymus in the establishment of suppressor cells in liver chimeras.
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Animals↗
Reconstitution of T cell function in patients with subacute sclerosing panencephalitis treated with thymus humoral factor.
Two patients with subacute sclerosing panencephalitis (SSPE) showed impairment of cell-mediated immunity, as indicated by a low T cell number, decreased intracellular cyclic AMP levels of peripheral blood lymphocytes, negative graft-vs.-host reaction in vivo, negative skin reactions to common antigens and, in one of the patients, abnormal reactions in migration inhibition factor tests. Since some of the impaired T cell functions in one of the patients were reconstituted in vitro by the administration of thymus humoral factor (THF), a thymic hormone shown in an earlier study to regulate maturation of T lymphocytes in in vitro and in vivo animal models, a course of THF administration was given to both patients in this study. In vitro and in vivo assays, which reflect T cell competence, were performed before and after a daily schedule of THF administration that lasted for 10 days in one patient and 21 days in the other. The results of this preliminary trial suggested that THF was capable of reconstituting the impaired T cell functions in both patients after a short term of treatment. These preliminary results should encourage additional long-term therapeutic trials with THF in SSPE patients with impaired cell-mediated immunity.
Animals↗
Trypsin-induced increase in intracellular cyclic AMP of lymphocytes.
Trypsin increases intracellular levels of cylic AMP (cAMP) in lymphocytes. The trypsin-induced increase in cAMP is blocked by specific trypsin inhibitors and by high concentrations of different proteins. Several proteolytic enzymes from various sources, including other pancreatic proteases, do not cause an increase in cAMP under the same experimental conditions. Immobilized trypsin induced the same increase in cAMP as does free trypsin. The trypsin-induced rise in cAMP is not due to inhibition of cAMP phosphodiesterase, but consistent activation of adenylate cyclase by trypsin could not be demonstrated. The extent of the trypsin-induced increase in intracellular cAMP correlates with the type of the lymphocyte and with the state of maturity attained by the cells. Transformed lymphocytes and nonlymphoid cells do not react at all.
Animals↗
Separation of populations of sensitized lymphoid cells into fractions inhibiting and fractions enhancing syngeneic tumor growth in vivo.
Separation of subpopulations of lymphoid cells sensitized against a syngeneic tumor was attempted by means of velocity sedimentation and the fractions were injected together with tumor cells into syngeneic hosts. Spleen cells from tumor-bearing mice or spleen cells sensitized on tumor cell monolayers could be fractionated into a subpopulation capable of inhibiting growth of the same tumor and a separable fraction which enhanced tumor growth. Activity of the tumor-inhibiting lymphocytes was not apparent in the presence of the tumor-enhancing cells. The former activity was associated with small lymphocytes and the latter with injection of larger cells. Preliminary experiments investigated the developmental relation between the cells responsible for these opposing activities.
Animals↗
Response of human lymphocytes to PHA and Con A, dependent on and regulated by THF, a thymic hormone.
The response of human lymphocytes to T lectins was shown to be dependent on and regulated by THF (thymus humoral factor). When human lymphocytes were stimulated with T lectins in the presence of dialyzed human plasma (DHP) which probably contains a low thymic hormone concentration, we observed a reduced response to PHA and Con A, compared to that observed in the presence of whole human plasma (WHP). This reduced reactivity to T lectins in the presence of DHP was restored by the addition of plasma dialyzates or THF. On the contrary, addition of THF to cultures in the presence of WHP caused a significant reduction in reactivity to T lectins, suggesting that enhancement or reduction of the response of human lymphocytes to T lectins by THF depends on the endogenous content of the thymic hormone in the plasma. From the present data it is suggested that the response of human cells to PHA behaves differently from that to Con A, as reflected in their dependence on THF. Although the response of human cells to Con A is increased by THF only in the presence of DHP, the response to PHA is also enhanced by THF in the presence of low WHP concentrations of even in the absence of WHP.
Concanavalin A↗
Recent studies on the role of the thymus in early stages of lymphopoiesis and immune differentiation.
The influence of thymus deprivation and thymus restoration was studied: a) on the cycling capacity of colony forming cells (CFU-S) in the bone marrow and b) on the establishment of tolerance in liver radiation chimeras. After neonatal thymectomy a reduction in the number of CFU-S in the bone marrow was observed. This reduction was accompanied by a striking decrease in the proportion of cycling cells in the bone marrow of thymus deprived mice. On the other hand, restoration of thymus function by thymic hormone (THF), by implantation of thymus in semi-impermeable cellophane bags, or by pregnancy, raised the number of cycling cells in the bone marrow to that of normal controls. Parental embryonic liver cells reconstitute lethally irradiated mice, and permit establishment of tolerance to further challenges of immunocompetent cells syngeneic to liver donors. We found here that adult thymectomy prevents the establishment of permanent tolerance in liver chimeras. Again, restoration of thymic function by THF permitted liver chimeric mice to resist the immunologic attack of parental spleen lymphocytes syngeneic to donor liver cells.
Age Factors↗
Inhibition of syngeneic fibrosarcoma growth by lymphocytes sensitized on tumor-cell monolayers in the presence of the thymic humoral factor.
The present experiments were performed to investigate the possibility of inhibiting tumor growth in vivo with syngeneic lymphocytes sensitized in vitro on monolayers of the tumor under test, and to study the effect of a thymic humoral factor (THF) in this sensitization process. Monolayers of fibrosarcoma cells were used to sensitize spleen cells from syngeneic donors against the tumor. Such sensitized lymphocytes manifested cytotoxic activity against cells fo the fibrosarcoma in a microassay measuring tumor-cell detachment. However, when the sensitized lymphocytes were mixed with the fibrosarcoma cells and injected into syngeneic mice, enhanced tumor growth was observed in vivo. Addition of thymic humoral factor to the cultures during sensitization resulted in increased cytotoxic activity by the lymphocytes in vitro and a reduction in the tumor enhancement caused by these cells when injected in vivo. Enhanced tumor growth occured when activated lymphocytes of allogeneic as well as syngeneic origin were injected together with the fibrosarcoma cells. Enhancement, which was already apparent when the spleen cells had been sensitized for 24 h, could be circumvented by separate administration of lymphocytes and tumor cells. Syngeneic lymphocytes injected systemically after sensitization for 5 days exerted anti-tumor reactivity against the fibrosarcoma grafted in the foot-pad of syngeneic mice. Tumor growth was further inhibited by systemic injection of lymphocytes which had been sensitized in the presence of the thymic humoral factor.
Animals↗