Effect of the thymus on the activity of immunoreactive peptides

Influence of the thymic gland on the biology activity of peptide mediators--cytomedins, has been studied in the content of different organs. The peptide which was obtained from the liver, spleen and muscle of sham-operated animals enhanced immune response on the sheep red cells, lengthened indexes of thromboelastography, and activated fibrinolysis after its administration to the thymectomized rats. The peptides from organs of thymectomized animals lost this ability. These findings confirm the hypothesis on the regulating function of the thymic gland in the synthesis and activity of cytomedins in the tissues.     

Palatine tonsils and immunity. VI. Effect of thymosin and palatine tonsil extract on the immunologic reactivity of neonatally thymectomized and intact mice]

Experiments were conducted on Wistar rats, intact and neonatally thymectomized CBA mice; a study was made of the immunological activity of the extracts of the thymus and the palatine tonsils of calves obtained by the method of Goldstein et al (1966). The extract of the palatine tonsils obtained proved to contain a small amount of thymosin at whose expense an insignificant restoration of immunological reactivity occurs in its administration neonatally to thymectomized mice.     

Thymic control of secretory antibody responses in the rat.

The effect of neonatal thymectomy on salivary and serum antibody responses was studied in rats. Local immunization of thymectomized rats with a T-dependent antigen (DNPBGG) elicited negligible amounts of IgA anti-DNP antibody in saliva. In contrast, both normal and sham-thymectomized animals demonstrated substantial levels of salivary IgA antibody. All thymectomized rats locally injected with a T-independent antigen (DNP-Lys-Ficoll) exhibited salivary IgA antibody production. Salivary IgG antibodies were somewhat decreased in thymectomized rats injected with either antigen; however, the final effect of T cell deprivation on IgG synthesis was not as pronounced as on IgA synthesis. Serum IgA antibody was induced in control rats injected with DNPBGG, whereas this Ig class of antibody was absent in thymectomized rats. The results suggest that thymus-derived cells exert a regulatory influence on both serum and secretory IgA responses to antigens.     

Studies of nonmigrating long-lived lymphocytes in rats. V. Presence and reactions to antigens after neonatal thymectomy

Neonatally thymectomized and sham-operated rats were given courses of hind foot pad injections of tritiated thymidine after immune stimuli, and the popliteal lymph nodes were examined for the presence of persistently labeled lymphocytes 32 days later. A larger proportion of labeled small lymphocytes was found in the nodes of thymectomized rats than in the nodes of sham-operated rats, indicating that a significant portion of the long-lived nonmigrating cells are B cells. In sham-operated rats given a course of tritiated thymidine after an immune stimulus with a Salmonella flagellin, labeled blasts appeared 3 days after secondary challenges with both the same or a serologically distinct flagellin. In neonatally thymectomized rats, a blastogenic response occurred after challenge with the same flagellin but not after challenge with the non-specific flagellin. Thus, in normal rats there are also long-lived nonmigrating T cells in primed lymph nodes, and these are the cells responsible for the nonspecific blasto-genesis seen in earlier experiments.     

The circulating life span, immunocompetence and 3H-uridine uptake of small lymphocytes from thymus-grafted, neonatally thymectomized rats.

By 7 weeks post-grafting, the number of small lymphocytes in the thoracic duct lymph (TDL) and blood of the thymus-grafted neonatally thymectomized adult rats had increased to 60% of the number of cells in sham controls, or 2-1/2 times thymectomized control values. This increasing consisted almost exclusively of long-lived, recirculating small lymphocytes and corresponded to a 60% recovery of cellular immunocompetence as measured by the mixed lymphocyte reaction (MLR). Associated with the return of cellular immunocompetence was an increased incorporation of 3H-uridine by the small lymphocytes. Cells from thymectomized animals grafted with lymph node fragments demonstrated no significant increase in lymphocyte numbers nor was there a return of immunocompetence as compared to thymectomized controls.     

Pubertal neurocranium growth in thymectomized rats

Differences in neurocranium growth at puberty were studied in rats of both sexes thymectomized and sham-thymectomized at 2, 4, 6, 8, 10, 12 and 14 days of age and in controls of matched age and sex; skull length, width and height, and skull base length and face length were measured. The neurocranium of the thymectomized rats was significantly smaller than that of the sham-thymectomized and control rats of both sexes and in all age-groups.     

Modulation by neonatal thymectomy of the reproductive axis in male and female rats during development

The effects of neonatal thymectomy, at 3 days of age, on parameters of the reproductive axis were examined in male and female Sprague-Dawley rats. Gonadal and accessory sex tissue (male: epididymis, seminal vesicle, and ventral prostate; female: uterus) weights as well as anterior pituitary, spleen, and adrenal weights were determined in the thymectomized and sham-thymectomized animals at 20, 30, 40, 50, 60, and 90 days of age. Plasma gonadotropin concentrations as well as pituitary content of the gonadotropins and prolactin were assessed at each of these time intervals. No significant difference in gonad and accessory sex tissue weights was detected in thymectomized versus sham-operated controls at each of these times. Adrenal weights were increased in thymectomized animals compared with controls at 50 days of age and older in male rats and at 90 days in females. Spleen weights were decreased in the thymectomized males at 50 and 60 days of age. Thymectomy did not affect the spleen weight of females. Plasma concentrations of gonadotropins were unaffected in thymectomized males but were altered in females during the pre- and peripubertal period (Days 20-40). Vaginal opening, however, occurred at the same time in the thymectomized and control females. Pituitary gonadotropin and prolactin content were unaffected by thymectomy of the females, except at 90 days when pituitary luteinizing hormone (LH) content was lower in thymectomized than in control animals. LH and prolactin content were significantly reduced in the males at 60 and 90 days of age. These results demonstrate that there are sexual differences in the effects of thymectomy on parameters of the reproductive axis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Trypanosoma cruzi: effects of anti-thymocyte serum in mice and neonatal thymectomy in rats

CF₁ mice were given eight injections of normal rabbit serum (NRS), Hanks' balanced salt solution (HBSS), or rabbit anti-mouse thymocyte serum (ATS) beginning 3 days prior to and at 3-day intervals subsequent to intraperitoneal (ip) inoculation with 5 × 10⁴ trypomastigotes of a Brazil strain of Trypanosoma cruzi. Markedly enhanced parasitemia, increased numbers of tissue stages (amastigotes), and higher mortality occurred in ATS-treated mice as compared to NRS- or HBSS-treated controls. Administration of three injections of ATS at 3-day intervals during the latter stages of acute Chagas' disease, i.e., when numbers of parasites were declining, resulted in a transitory relapse (increase in numbers) of blood and tissue parasites. No relapse occurred in mice when ATS was administered at 3-day intervals over a period of 15 days during the subacute stage of the disease, i.e., after parasites had disappeared from the blood.Parasitemia and mortality were enhanced in neonatally thymectomized rats when compared to that observed in sham-operated and unoperated control rats following ip injection of 2 × 10⁵ trypomastigotes of T. cruzi. Serum obtained from thymectomized and control rats 5 weeks after inoculation with T. cruzi at a time when the blood of all animals had become microscopically negative for parasites were equally protective in passive transfer experiments, while serum from uninfected controls gave no protection.Gamma globulin levels significantly increased in thymectomized as well as intact rats by the third to fourth week of infection with T. cruzi, reached maximum concentrations in 5–6 wk, and remained elevated significantly at the twelfth week post infection as compared with uninfected controls. No significant changes occurred in total serum proteins or α and β fractions of any group, infected or uninfected.Total circulating leukocytes, especially lymphocytes, were diminished in mice and rats subjected to treatment with ATS or neonatal thymectomy.These data clearly indicate that neonatal thymectomy of rats and ATS treatment of mice suppress the acquired immune response to T. cruzi. Further, passive transfer experiments in rats confirm the protective role of circulating antibody in acquired immunity to Chagas' disease.     

Mitogenic factor from inbred guinea pigs. II. Properties of the factor

Thymectomized adult rats which have been heavily irradiated and reconstituted with syngeneic bone marrow cells rapidly regain the ability to defend themselves against a primary infection with the intracellular bacterial parasite, Listeria monocytogenes. They do so by a cell-mediated immunological mechanism as evidenced by the protective immunity transferred adoptively by thoracic duct lymphocytes or peritoneal exudate cells from donors infected with this organism. But peritoneal exudate cells from thymus-derived donors convey only a fraction of the immunity transmitted by exudate cells from similarly infected intact rats. Since thymectomized irradiated animals can mobilize their cellular defenses more effectively when they are injected with a modest number of thoracic duct lymphocytes, an effect that cannot be duplicated with a massive infusion of bone marrow, it is argued that thymusdependent lymphocytes or T cells have an influential role in the development of cellular resistance to infection.     

Study of the thrombolytic and fibrinolytic properties of thiol- dependent serine proteinase (TSP) from Thermoactinomyces vulgaris in vivo

Experiments on male albino rats showed that the thyol-dependent serine proteinase (TSP) dissolved the thrombus in the jugular vein for 2-5 hr. Intravenous injection of TSP activated the fibrinolytic system of intact animals by increasing the levels of the plasminogen activator and plasmin in the euglobulin fraction. The response of the fibrinolytic system on the intravenous injection of TSP (2mg/200 g) was different: in some rats, fibrinolysis was activated, while on others, it was inhibited. TSP in high doses caused the death of 60% of experimental animals.     

Radiosensitivity of a thymocyte subpopulation capable of stimulating erythropoiesis in locally irradiated animals

It was shown that, in contrast to intact thymocytes and to those irradiated with a dose of 0.25 Gy, thymocytes exposed in vivo to doses from 0.5 to 1.5 Gy and transplanted to locally irradiated (7 Gy) thymectomized BALB/c mice failed to stimulate the recovery of the erythron.     

Thymectomy should be the first choice in the protection of diabetes-prone BB rats for breeding purposes

Diabetes-prone (DP)-BB rats spontaneously develop diabetes and are widely used as an animal model for the study of type 1 diabetes. Since DP-BB rats develop diabetes before or at the time of breeding, such rats used for breeding need to be protected against diabetes development by the transfer of regulatory T cells obtained from diabetes-resistant (DR)-BB rats, by insulin treatment or by thymectomy. Thymectomy of juveniles is not commonly used to protect DP-BB rats, and we investigated whether breeding with thymectomized DP-BB rats was a realistic alternative to the two other methods. No differences in pregnancy rates, numbers of pups per litter or growth rates of pups were found. Moreover, no differences were found in diabetes development in the offspring. Protection of juvenile DP-BB rats by thymectomy is comparable to the other established procedures, is simple and safe, and the rats recover well from the procedure. Breeding with thymectomized animals will reduce the number of animals needed, and it improves the well-being of the animals because it reduces the negative side effects associated with the other procedures such as episodes of hypo and hyperglycaemia. Therefore, although thymectomy is an invasive procedure, we would like to recommend weanling thymectomy as the first choice for the protection of DP-BB rats for breeding purposes.     

Effect of Chemical Thymectomy on Skin Homografts: A Preliminary Report

In an attempt to combine the results obtained by Miller (mice thymectomized at birth accepted homograft at six weeks of age) and those obtained by Selye (selective calcification of the cortex of the thymus with calciphylaxis), calcification of the thymus was produced by the combined injection of dihydrotachysterol and triamcinolone, in non-inbred Sprague-Dawley and hooded, eight-week-old rats. Six days after the beginning of treatment, full-thickness skin homografts were performed on the rats.Homografts exchanged between two rats with complete calcification of the thymus cortex were accepted for an extended period of time, which in the oldest rats at the time of writing was seven months. Homografts exchanged between rats with incomplete calcification of the thymus resulted in a prolonged homograft survival with final rejection within a period of three weeks. Homografts exchanged between rats that were not treated, surgically thymectomized at the same age as the treated animals, or treated with only one of the two substances used for thymus calcification, resulted in rejection in the average time of eight days.     

The role of the active center of the enzyme in the triggering mechanism of the compensatory reaction to plasmin

The participation of plasmin active site in the trigger's mechanisms of the compensatory reaction of haemostasis system on this enzyme was studied in the experiments on white rats and rabbits using intravenous injection and perfusion of the humorally isolated carotid sinus are with intact innervation. Native enzyme, the enzyme with reversibly (acylated plasmin) and irreversibly (diisopropylphosphoryl plasmin) blocked active site were used. It was ascertained that the development of the compensatory reaction of haemostasis system on plasmin, manifested by hypercoagulation and depression of fibrinolysis, is conditioned by the proteolytic activation of the vascular wall receptors.     

Fluctuations in pulmonary fibrin decomposing activities (plasmin and non-plasmin activities) in an endotoxin DIC model in rats

Non-plasmin fibrinolysis enzyme was extracted from the lung and spleen of conventional rats (Thrombos. Haemostas., 1979), although the enzyme was not found in germfree rats, suggesting the possibility that the enzyme may participate in the defence mechanism of the body. The present study was made in an attempt to determine the behavior of non-plasmin fibrinolysis enzyme of the lung tissue in the DIC model of conventional rats induced by a single injection of bacterial endotoxin. The plasminogen-activator activity of the lung tissue, and the fibrinogen level, platelet count, urea nitrogen and plasminogen-activator activity in the blood were also measured. Examination of the lung tissue in the DIC rats indicated a remarkable increase in non-plasmin fibrinolysis activity and a disappearance of plasminogen-activator activity. Inhibitor studies using t-AMCHA and DFP demonstrated that the increased non-plasmin fibrinolysis activity was not derived from activated plasmin, but from serine protease. The disappearance of plasminogen-activator activity in the lung and increase of plasminogen-activator activity in the blood suggested a release of the activator from the lung into the blood due to the endotoxin injection.     

Physiological dependency between the hypothalamus and the thymus in Wistar rats. II. The neurosecretion level and microstructural changes following para-chlorophenylalanine administration. The differences in DL-5-hydroxy G-3H tryptophane incorporation in the hypothalamus of normal and thymectomized rats

The experiments were carried out on male Wistar rats, both normal and thymectomized in which the thymus was excised in 12th h of life. 8 weeks later, the animals were administered parachlorophenylalanine [PCPA], i.e. a compound inhibiting tryptophane hydroxylase, in the amount of 200 mg/kg of body weight. The studied hypothalamus preparations, i.e. supraoptical [NSO] and paraventricular nuclei [NPV] revealed an increased level of Gomori-positive neurosecretory material in thymectomized rats when compared to control animals. It was observed that the former rodents manifested an elevated incorporation of the isotope, i.e. DL-5-Hydroxy [G-3H] Tryptophane. The calculations performed by the use of the Gosset's t-test ("Student's") showed that the difference was statistically significant (p less than 0.001).     

Effect of T-cell mitogens and T-lymphocyte deficiency on splenic colony formation

A study was made of the influence of T-cell mitogens (Con A and PHA) on the colony formation and differentiation of hemopoietic stem cells from normal and thymectomized mice, as well as of the relationship between the colony formation and the dose of injected thymocytes. The incubation of bone marrow cells with Con A and PHA was shown to inhibit the growth of spleen colonies. This inhibition is reduced by thymocytes within the dose intervals of 0.25-2.0 X 10(7) cells/mouse. Administration of these agents serially has led to the potentiation of inhibition effect and to the inability of thymocytes to reverse it. Con A and PHA exert no effect on the differentiation of stem cells. Incubation of the bone marrow cells from thymectomized mice with Con A is much less effective in the depression of colony formation, if compared with the treatment by intact bone marrow preparations. A reversed picture was observed using antiserum to mouse brain (RAMBS). It is proposed that regulation of stem cells is governed by different subpopulations of thymocytes.     

Neonatal thymectomy affects follicle populations before the onset of autoimmune oophoritis in B6A mice

Using a variation on a standard follicle classification technique, 5 classes of follicles were quantified in serial sections of ovaries from intact mice and mice thymectomized on Day 3 at 5-day intervals from 5 to 40 days of age. Sera from these animals and from animals 60 days of age were analysed for the presence of anti-oocyte antibodies. Ovaries from intact animals 10 to 40 days of age were examined for the presence of antigen(s) using anti-oocyte antibody-positive sera from all ages of mice. There was a dramatic decrease in the primordial follicle population at 10 days of age in thymectomized mice and that population remained significantly lower until 40 days of age. The growing follicle population was also significantly lower at 20 days of age in thymectomized mice and remained lower through 40 days of age. Anti-oocyte antibodies were not detectable until 30 days of age and at that age reacted with oocytes from all follicle types including primordial. Ovarian antigens were present in similar patterns in ovaries from mice at all ages tested. We conclude that thymectomy has an earlier influence on the ovary than previously thought and this influence does not appear to involve the immune activity associated with autoimmune ovarian dysgenesis. This suggests that the effect of thymectomy on the ovary may be biphasic: (1) an early effect, possibly involving a disruption in the hypothalamic-pituitary-ovarian-thymic axis, that influences the primordial and growing follicle populations before 20 days of age; and (2) a later effect involving an immune imbalance first evident by 25-30 days of age that ultimately results in the destruction of the ovary.     

Effect of T-activin on peripheral immunity organs in intact and thymectomized mice

Morphometry of the spleen, axillary lymph nodes and cytological assay of the bone marrow and peripheral blood were performed in (CBA X C57BL)F1 mice 1, 5, 10 and 15 days after subcutaneous injection of 0.5 microgram T-activin to intact and thymectomized (when adult) mice 2 months after operation. It was demonstrated that in intact animals, injection of T-activin stimulated the whole system of immunogenesis. The time course of plasmatization and the response of the germinative centers differing from that seen during antigen administration suggests that T-activin is not immunogenous, acting as a stimulant of the previous immune responses. The permanent amount of the degenerating cells attests to the lack of the toxic drug effect.     

Change in the reaction of circulating colony forming units to ACTH in thymectomized mice

It has been discovered that unlike animals with the intact thymus, thymectomized adult (CBA X C57B1)F1 mice did not demonstrate any reduction in the number of circulating colony-forming units (CFUs) induced by the elevated concentrations of endogenous glucocorticoids 2 weeks to 5.5 months following operation. It is assumed that the effect of glucocorticoids on CFUs is mediated by the T1 lymphocyte subpopulation.