Effects of hormones on development and function of lymphoid tissues: Synergistic action of thyroxin and somatotropic hormone in pituitary dwarf mice

Hereditary pituitary recessive dwarf mice of the Snell—Bagg strain were used in the present experiment to study the effects of thyroxin and somatotropic hormone alone or in combination, on morphology and immunological function of lymphoid tissues and bone marrow. These animals are characterized by early involution of the thymus, cellular depletion in the peripheral lymphoid tissues particularly evident in the medullary cords and by marked signs of hypocellularity in the bone marrow. They also show an evident depression of the primary immune response to sheep erythrocytes (SRBC). Treatment with the hormones, mainly in combination, prevents the thymus involution, the cellular depletion in lymph nodes and induces signs of cellular repopulation in the bone marrow. Only the combination of both hormones completely normalizes the humoral response to SRBC. It is suggested that the primary site of action of the tested hormones is in the bone marrow. As a result, both antigen-sensitive and antibody-producing cells may be affected through their cellular precursors in the marrow.     

Regeneration of thymus grafts. II. Effects on immunological capacity

Mice thymectomized at birth were grafted at 1 week of age with thymus tissue under the kidney capsule. The implants were excised after a period of 1, 2 or 3 weeks and the response of the mice to sheep erythrocytes and to allogeneic skin grafts was tested. Thymectomized mice that had not received thymus implants had twenty times less antibody-plaque-forming cells per million spleen cells than sham-thymectomized controls and failed to reject foreign skin. Some evidence of restoration of immune capacities was obtained in mice bearing for 1 to 2 weeks either normal thymus implants or thymus tissue irradiated in vitro with 500 R. By contrast, thymus tissue irradiated with 2000 R failed to influence neonatally thymectomized mice with respect to their immunological capacities. Most thymectomized mice bearing thymus implants, whether normal, irradiated with 500 or 2000 R, had blood lymphocyte levels within the normal range. Cytological analysis of the lymph nodes and spleen of mice bearing normal thymus implants revealed only very few thymus-derived cells but the proportion of these cells was significantly increased after specific immunization. No thymus-derived cells were however detected in the lymphoid tissues of mice bearing irradiated thymus implants, not even in those that were capable of responding to antigenic stimuli. It is concluded that the thymus plays an essential role in inducing the differentiation of immunologically competent cells from non-competent precursors and that this function is dependent on the integrity of the thymus epithelial-reticular cells.     

Delayed development of immunological responsiveness in neonatally thymectomized mice: a time-course study

Haemolysin responses to first injection of sheep erythrocytes in neonatally thymectomized, neonatally sham-thymectomized and intact Swiss albino mice were tested when the mice were 10 days, 4 weeks, 6–7 weeks and 6 months of age. The serum haemolysin activity was assessed at a number of times after injection of antigen (time-course study). Neonatal thymectomy of Swiss mice was followed by a decreased and delayed haemolysin response. These abnormalities in antibody response following neonatal thymectomy became less obvious when the age at which the mice were injected was increased, indicating that delayed development of immunological responsiveness had occurred in neonatally thymectomized Swiss mice.     

T and B lymphocytes in pituitary dwarf Snell-Bagg mice.

The lymphocyte composition of the thymus and spleen from weaned (4 month old) hypopituitary dwarf Snell-Bagg mice were compared to those of their phenotypically normal littermates and of hormone (somatotropic hormone plus thyroxine)-treated individuals. Detection of cells bearing receptors for peanut agglutinin, physical analysis and measurement of in vitro reactivities to phytohaemagglutinin and concanavae intra-thymic lymphocyte population of dwarf mice. Examination of spleen-cell suspensions demonstrated a slightly higher frequency of T lymphocytes (Thy 1-2+ alpha-Naphthyl esterase+, high electrophoretic mobility) and lower frequency of B lymphocytes (surface immunoglobulin+, low electrophoretic mobility) in dwarf mice than in control mice. The degree of splenocyte responsiveness to T- and B-cell mitogens, however was similar in the two mouse types. High mobility (T) splenic cells were found to exhibit a smaller modal volume in dwarf mice (110 micron3) than in control mice (122 micron3) but this difference was not corrected by hormone administration. More pronounced were the quantitative differences between the spleens of hormone-deficient and normal mice. Thus, when expressed as a function of body weight, the numbers of splenic T and B lymphocytes in untreated dwarf mice were about half the corresponding values in hormone-reconstituted or normal littermates. These data suggested that in adult life, developmental hormones exert little direct effect on the thymus lymphocytes but influence the size of the pool of both peripheral T and B lymphocytes.     

Peripheral lymphoid development and function in TCR mutant mice

We describe the development and function of the peripheral lymphoidsystem of mutant mice rendered deficient in either ßor T cells via targeting of TCR genes In embryonic stem cells.In the spleen of ß T cell-deficient mice, T cellsdo not compensate in numbers for the lack of ß Tcells, but B cells do. ß T cell-deficient mice areunable to mount an antibody response to ovalbumln and do notreject skin allografts. Natural killer cell function is notimpaired in any of the mutant mice. TCR mutant mice will proveuseful in dissecting differential functions of ßand T cells in vivo.     

Hormones and the immunological capacity. IV. Restorative effects of developmental hormones or of lymphocytes on the immunodeficiency syndrome of the dwarf mouse

The restorative action of developmental hormones, mainly somatotropic hormone, and of lymphnode lymphocytes on the immunologically crippled hypopituitary Snell-Bagg dwarf mouse is evaluated. The hormonal treatment can completely reconstitute the structure of the thymus and of the peripheral lymphoid tissues. Both hormones and mature lymphocytes restore the impaired capacity of the dwarf mouse to propuce antibody and to reject skin allografts. Normal donor thymocytes and bone marrow cells alone or in combination fail to produce the same effect in absence of a hormonal treatment. The action of hormones is not exerted if dwarf mice are thymectomized in adult age. This and other evidence shows that the action of hormones is mediated through the thymus and leads to the formation of long-living lymphocytes.     

Delayed development of primary immunological responsiveness in neonatally thymectomized swiss albino mice

Neonatally thymectomized Swiss mice exhibit a delayed development of immunological responsiveness. The behaviour of 19S and 7S haemolysin during the response that eventually arises in thymectomized mice is consistent with that of a primary response with the major abnormality being the delayed production of maximal amounts of 7S haemolysin.     

Effects of exogenous melatonin on pituitary hormones in humans.

The effects of melatonin on physiological function remain unclear, although the therapeutic potential of melatonin is being increasingly recognized. The aim of the present study is to investigate the effects of exogenous melatonin on the spontaneous release of pituitary hormone in humans. A double blind placebo-controlled protocol was designed to examine 12 adult healthy volunteers and 12 sleep disorder patients who have been treating with low doses of melatonin for 1 year. Either exogenous melatonin or placebo of 1 mg was given at 09:00 hours, followed by the collection of blood samples every 20 min for 4 h. Each blood sample was examined for levels of serum melatonin, PRL, LH, FSH, GH and TSH. LH levels were higher in sleep disorder patients compared with the healthy volunteers. In other pituitary hormones, there were no significant difference between healthy adults and sleep disorder patients. In all subjects, PRL levels were stimulated by acute administration of 1 mg of exogenous melatonin, while the levels of other pituitary hormones were not affected. These results suggested that exogenous melatonin can affect the spontaneous release of LH and PRL in humans. In addition, we demonstrated that 1-year oral melatonin treatment did not affect the responses to the acute administration of melatonin.     

The development and function of mucosal lymphoid tissues: a balancing act with micro-organisms

Mucosal surfaces are constantly exposed to environmental antigens, colonized by commensal organisms and used by pathogens as points of entry. As a result, the immune system has devoted the bulk of its resources to mucosal sites to maintain symbiosis with commensal organisms, prevent pathogen entry, and avoid unnecessary inflammatory responses to innocuous antigens. These functions are facilitated by a variety of mucosal lymphoid organs that develop during embryogenesis in the absence of microbial stimulation as well as ectopic lymphoid tissues that develop in adults following microbial exposure or inflammation. Each of these lymphoid organs samples antigens from different mucosal sites and contributes to immune homeostasis, commensal containment, and immunity to pathogens. Here we discuss the mechanisms, mostly based on mouse studies, that control the development of mucosal lymphoid organs and how the various lymphoid tissues cooperate to maintain the integrity of the mucosal barrier.     

Effects of cyclosporin A on mouse lymphoid tissues.

Cyclosporin A (CsA) was administered s.c. to BALB/c and C3H mice for periods up to 25 days and the effects were monitored by the immune response to SRBC, HGG, and B. abortus. Whereas the rate of growth of BALB/c mice was only depressed after the 20th day, C3H mice lost weight from the start of treatment. In both strains there was no change in the weight of the spleen and mesenteric lymph node but the thymus weight decreased markedly. This decrease in thymus weight was accompanied by thymic involution with little or no change in spleen or mesenteric lymph node. An increase in Mott cells, as so strikingly demonstrated in the CsA-treated chicken (Nowak et al., 1982), was dependent on the degree of thymic involution. When the thymus was normal in appearance there was a slight increase in the number of splenic Mott cells, when compared with untreated controls; in the more usual case of thymic involution (or necrosis), there was no increase in the number of Mott cells.     

番茄红素对实验小鼠免疫功能的影响

目的:应用中药血清药理学方法,观察番茄红素对实验小鼠免疫功能的影响。方法:用6周龄,体重为18~20g的BALB/c小鼠200只,设0、10、15和20 mg/kg.bw四个番茄红素水平处理。于给药后0.5、1、1.5、2、2.5、3、3.5、4、4.5和5小时分别无菌条件下取血,分离血清进行脾脏T细胞增殖活性和分泌IL-2、IL-4活性、NK细胞杀伤活性等免疫功能检测。结果:不同剂量番茄红素对脾淋巴细胞增殖、IL-2、IL-4产生有促进作用,且不同时相有所波动;能明显增强NK细胞活性,以高剂量组最为明显,作用时间较长;其药效影响集中在给药后0.5~3小时。结论:适宜剂量的番茄红素能增强特异性与非特异性免疫,表明有提高机体免疫功能的作用。     

Hormones and the immunological capacity. III. The immunodeficiency disease of the hypopituitary Snell-Bogg dwarf mouse

The naturally occurring immunodeficiency syndrome of the hypopituitary Snell-Bagg dwarf mice has been characterized. The immunopathological aspects of this syndrome derive primarily from an arrested ontogenetic development of the thymus. The alteration of the thymus function is caused by the failure of the pituitary to produce certain hormones, especially somatotropic hormone. The relation of this syndrome of the dwarf mouse to human immunodeficiency diseases and endocrinopathies is discussed.     

Small lymphocytes in peripheral lymphoid tissues of nude mice. Life-span and distribution.

The distribution of small lymphocytes according to life-span in the peripheral lymphoid tissues of the mouse mutant "nude" has been studied by means of auto-radiography and scintillation counting to evaluate the localization of B lymphocytes with varying life-span. The vast majority of the lymphocytes in this congenitally athymic mouse are relatively long-lived, although few cells live for 6 weeks or more. Differences in labelling percentages of blood, spleen and lymph node lymphocytes indicated a production of lymphocytes with a short residence time in the spleen. A similar production was not seen in the lymph nodes. While the lymphocytes in the spleen were evenly distributed according to life-span, the paracortical lymphocytes in lymph nodes were found to have a generally shorter life-span than those of the cortex, in opposition to findings in normal mice. The cortical cells which were by far the most numerous in the lymph nodes seemed to be more sessile than para-cortical lymphocytes. The life-span of these latter cells are comparable to those of thoracic duct lymphocytes, and the scarcity of cells in the paracortex reflects the small number of recirculating lymphocytes in nude mice.     

车前多糖对小鼠免疫功能的影响

车前子为车前科植物车前的干燥成熟种子.中国药典记载[1],车前子药用有2种,即车前(P.asiatica L.又称大粒车前)和平车前(P.depressa Willd.又称小粒车前).车前子种皮中含有大量的粘液质.我国目前临床和民间多将种皮中的粘液质弃而不用,种皮中的多糖成分一直未被研究.本课题组对吉安车前研究发现,该车前子含有丰富的多糖成分[2].本文研究了吉安车前种皮粘液质中的精制多糖对小鼠免疫功能的影响,可为开发其新的临床应用提供理论依据.     

Effects of cyclosporin A on mouse lymphoid tissues

Cyclosporin A (CsA) was administered s.c. to BALB/c and C3H mice for periods up to 25 days and the effects were monitored by the immune response to SRBC, HGG, and B. abortus. Whereas the rate of growth of BALB/c mice was only depressed after the 20th day, C3H mice lost weight from the start of treatment. In both strains there was no change in the weight of the spleen and mesenteric lymph node but the thymus weight decreased markedly. This decrease in thymus weight was accompanied by thymic involution with little or no change in spleen or mesenteric lymph node. An increase in Mott cells, as so strikingly demonstrated in the CsA-treated chicken (Nowak et al., 1982), was dependent on the degree of thymic involution. When the thymus was normal in appearance there was a slight increase in the number of splenic Mott cells, when compared with untreated controls; in the more usual case of thymic involution (or necrosis), there was no increase in the number of Mott cells.