Effect of T-activin on thymus involution in mice

The effect of T-activin on thymus involution in mice was studied. T-activin in a dose of 1.0 micrograms/mouse was injected into young male (CBA X C57BL)F1 mice weighing 24.0 +/- 2.0 g daily for 20 days. Morphometric analysis of the thymus was made 6 months after the treatment with T-activin was completed. It was found that T-activin induced the suppression of physiological involution of the thymus together with the enhancement of the processes of thymocyte transformation and proliferation.     

Interaction of T-activin with peritoneal macrophages

The action of T-activin on peritoneal macrophages of CBA mice after its introduction into the animals has been studied. In intact mice the phagocytic activity of macrophages and their resistance to the cytopathogenic action of Salmonella typhimurium live cells remains unchanged. The injection of corpuscular pertussis vaccine into mice leads to a decrease in the resistance of macrophages to the action of salmonellae. The simultaneous injection of T-activin into mice in doses of 0.1 and 1.0 microgram per animal abolishes the damaging action of the vaccine. The analysis of the in vitro action of T-activin on macrophages of intact mice revealed that the preliminary incubation of cells with the preparation sharply increases their resistance to the action of salmonellae, while its introduction simultaneously with bacteria or after them rapidly leads to the death of macrophages. The action of T-activin is supposed to be linked with triggering the biosynthetic processes mediating the resistance of macrophages to the cytopathogenic action of salmonellae.     

The use of T-activin for the prevention of congenital influenzal infection in mice and the correction of the immune deficiency

Viremia accompanying influenza infection and the possibility of transplacental passage of the virus into the fetus make it expedient to develop measures for the prophylaxis of intrauterine infection of the fetus in case of influenza during pregnancy. The work presents the optimum scheme of administration of T-activin for prophylactic purposes to pregnant mice with acute influenza infection. Besides, the use of T-activin for immunocorrection in case of established congenital influenza infection in mice is proposed.     

Nonspecific immunomodulation influences resistance of mice to experimental infection with Mesocestoides corti and Ascaris suum

The influence of nonspecific immunomodulation on the course of experimental infection was examined in larval cestodosis (Mesocestoides corti) and ascaridosis (Ascaris suum) in mice. Immunosuppressive treatment (with azathioprine or hydrocortisone) resulted in a decrease of resistance in both models. The subsequent administration of T-activin to immunosuppressed mice led to the restoration of resistance to a level equal to that of untreated control mice. The administration of different immunomodulators partially protected mice against M. corti (T-activin, thymomodulin) or A. suum (T-activin, thymomodulin, thymosin fr.5, bursa-activin) infection. The protective effect of different treatments did not correlate with the level of specific antibody in the sera of infected mice. These results, which confirmed the decisive role of T-cell immunity in the resistance to the helminth infections, raise the possibility of the use of immunomodulators (thymic preparations) in the immunoprophylaxis of helminthoses.     

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.     

Effects of T-activin on the morphology of the thymus gland in experimental injury of the lower limbs in mice (anti-stress effect of T-activin)

The effect of T-activin on thymic involution under the experimental trauma of femur was studied. T-activin in a dose of 1.0 micrograms/mouse was injected into young male (CBA X C57BL)F1 mice weighing 17.5-19.0 g before (I injection) or immediately after the fracture of the femur during 3 days. Morphometric analysis of the thymus was made 1, 5, 10 and 15 days after the trauma. It was found that T-activin suppressed the involution of the thymus, induced by the trauma, during the first 5 days and accelerate the process of its regeneration. It is suggested, that T-activin displays protective anti-stress effect on the mouse thymic involution.     

Change in immunological and biochemical parameters in germ-free animals in response to T-activin

The influence of immunoregulating humoral thymus factor T-activin (fraction AFT-6) on the activity of xenobiotic metabolism enzymes (EMX) and cellular-dependent cytotoxicity was investigated in germ-free guinea-pigs. Germ-free and conventional animals were injected 5 micrograms of T-activin intraperitoneally, on 3 successive days. The control animals were injected a physiologic saline. A day after the last injection the animals were killed, and EMX and K cell activity was measured. It was found that EMX activity in germ-free animals was decreased. T-activin stimulated cytochrome P-450, NADP-cytochrome-C-reductase, glutathione-S-transferase, benzopyrene hydroxylase and epoxyhydrase activity. In conventional animals the activity of these enzymes remained unchanged under the influence of T-activin. K-cell activity in germ-free animals was decreased, as compared to conventional guinea-pigs. Under the influence of T-activin the parameter increased and stood at about 70% of normal values.     

Effect of T-activin on thymocyte reproduction and migration

Forty seven F1 (CBA X C57Bl) mice were used for quantitative morphologic examination of the thymus on 1, 5, 10 and 15 days after a single injection of 0.5 microgram T-activin, and injections of 0.1 microgram of T-activin once a day during 5 days. The number of transformed thymocytes and mitoses figures in cortex was found to be increased reaching a maximum at the 5th day as regards the magnitude and spreading. By the end of the research the number of transformed thymocytes and mitoses returned to initial values. There was a periodical (at the 5th and 10th days) 1 mm2 reduction in the number of thymocytes, an increase in the proportion of medullary thymocytes, reaching maximum at the 5th day, and a tendency towards the reduction of a relative area of the parenchyma. These indicators did not return to the initial values by the 15th days. However there was a tendency towards normalization. The conclusion is made about the stimulatory effect of T-activin on reproduction and migration of thymocytes.     

Cell proliferation in mouse tissues after thymectomy and the administration of T-activin

The epithelium of mouse cornea and lymph nodes was examined for DNA-synthetic and mitotic activity at different times after thymectomy and administration of T-activin, an active factor of the thymus. Thymectomy entails retardation of the rate of corneal epithelium regeneration, diminution in both tissues under study of the amplitude of oscillations in cell proliferation throughout the day. Administration to the animals of the immunoactive thymic factor T-activin makes the circadian rhythm of cell proliferation return to normal. It is assumed that T-activin raises the capacity of lymphocytes to interact with epithelial cells, which manifests itself in the enhancement of their mitotic activity.     

Study of the action of immunomodulator T-activin on electric properties of plasma membranes of thymus cells by the use of fluorescent probes

T-activin alters the electric properties of plasmatic membranes of the T-activin treated suspension of mouse (CBAX X057B1) F1 thymic cells. These alterations were registered by means of negative charged fluorescent probe l-anilino-naphthalene-8-sulfonate (ANS) and positive charged 4-(p-dimethylaminostyryl)-1-methylpyridinium (DSM) by measurement of their fluorescence in the individual thymic cell. Apparently, T-activin leads to depolarization of transmembrane potential on plasmatic membrane of thymic cells. It seems that action of T-activin is similar to the effect of polycations, which alter cells ionic streams during lymphocyte activation. However, there is a version, that T-activin acts like neuraminidase, but it is activity less expressed.     

Effect of T-activin on the production of immune interferon

A study was made of the effect of T-activin on the biosynthesis of immune gamma-interferon. It was shown that in 27% of patients with chronic nonspecific pulmonary diseases, production of gamma-interferon by lymphocytes was substantially reduced during exacerbation of inflammatory process in the lungs. It was discovered that T-activin was not an interferon inductor but enhanced its synthesis in patients with a low capacity of producing immune interferon even at small doses of interferon inductor. The preparation does not produce any effect on this process in normal subjects and in patients showing the normal level of gamma-interferon. Thus T-activin can be used for stimulation of interferonogenesis.     

The effect of using T-activin in the therapy of the newborn with suppurative surgical infection

A total of 156 newborn infants with suppurative surgical infection (SSI) were observed; 73 of them had sepsis and 83 a severe localized process. In 47 patients with sepsis and 34 with localized infection, T-activin was included in complex therapy while the other infants formed the control group. It has been established that T-activin leads to an increase in the quantity of the active population of T-lymphocytes in the peripheral blood and to enhanced functional activity of T-lymphocytes in the newborn with SSI independent of generalization of the process. Bactericidal activity of circulating phagocytes is improved. The clinical course of SSI is less severe with more pronounced positive changes in the symptoms, hospital stay of the children is shortened, lethality is reduced. The effect of T-activin on the dynamic of the indices of the immune state is more marked in a septic process.     

Effect of T-activin on the formation of conditioned reflex and manifestations of unconditioned reflex of avoidance in August strain rats]

It has been revealed that intraperitoneal injection of T-activin (humoral factor of the thymus) to August rats leads to more rapid and stable conditioned reflex formation to a sound and to a decrease of avoidance time when electric current is given to a shuttle chamber. Furthermore, less amount of uneffective series in testing unconditioned avoidance is registered in the test animals. A positive T-activin effect on conditioned reflex formation and unconditioned reflex manifestation is probably connected with its ability to alter hippocampus functional parameters and (or) with anti-stressor properties of the preparation.     

Action of T-activin on human natural killer activity in vitro

The activity of natural killers (NK) from human peripheral blood was determined by 3H-uridine test using target cells K-562. T-activin effect on the activity of human NK in vitro depended on two parameters: the preparation dose and effector/target cells ratio. The inhibitory effect of T-activin was observed with high doses and increased E/T ratio, while the activating effect was noted with low doses and reduced E/T ratio. This can be attributed to the heterogeneity of NK population, different functional role of high and low doses of thymic factors and the development of NK as T-cell precursors.     

Effectiveness of correcting radiation injuries of the thymic endocrine function by T-activin in conditions of reduced postradiation hypercorticism reaction]

T-activin administered to rats after exposure to whole-body 1.5 Gy neutron- and 6 Gy X-radiation increases considerably the thymosin-like serum activity, accelerates cellularity restoration in the thymus and spleen, but does not influence the survival rate. Ionol administered prior to X-irradiation reduces the postirradiation hypercorticism reaction and the indirect effect of radiation on lymphoid organs which it is responsible for. The combined injection of ionol and T-activin increases the thymosin-like serum activity and spleen cellularity to the highest possible level and increases the survival rate of rats from 24 to 64 per cent and the lifespan up to 6 days.     

The dose dependence of various loads using the rosette formation method

A method of the loading tests in rosette-formation was used to study the rosette-formation of lymphocytes and phagocytosis of neutrophils depending on different concentrations of T-activin (and levamysol) after preincubation of leucocytes in vitro with these medicines. It is shown that significant effect of the cells is observed up to the concentrations of the medicines 10(-10)-10(-13) g/l.     

Immunochemical identification and study of interspecies thymus antigen-2

A new interspecific animal thymus antigen (AgT-2) was identified. It was shown that AgT-2 is a microglobulin with a molecular mass about 12 kDa, electrophoretic mobility of alpha 1-globulins and isoelectric point of 4.6. Heating of the protein to 80 degrees C for 30 min did not lead to the loss of its immunochemical activity. AgT-2 was identified in extracts of bovine fetal thymus, spleen and liver. It was discovered in the extracts of the lung and colon of adult animals. Cross-reactions were found between bovine, walrus, deer and chicken AgT-2. This fact confirms that AgT-2 is interspecies-specific. AgT-2 was not identified in men, dogs, mice, rats and rabbits. Immunochemical research of immunocorrecting preparations revealed that AgT-2 is a constant component of T-activin, thymalin, thymosin and TP1-Serono and its concentration varies from 1.6 to 3.2%. It has been stated that immunochemical test for AgT-2 can be used as a marker in the production and standardization of active thymus factors.     

Interactions of interferon with other immunomodulators in the regulation of human natural killer cell activity]

The cytotoxic activity of natural killer (NK) cells isolated from peripheral blood of 20 healthy donors and 34 patients with multiple sclerosis (MS) against labelled with H3-uridine target cells K-562 before and after their 1 hr treatment with reaferon (RF), T-activin (TA), myelopid (MP), opioid preparation dalargin (DL) as well as with combinations of TA, MP and DL with RF was studied in 14 hrs cytotoxic test. It has been shown that combination of RF with TA, MP and DL changed the regulatory action of these peptides on NK cell activity in healthy donors in vitro. The same combination of the preparations in patients with MS caused another changes in regulation of NK activity by them because NK cells in MS patients had had initially changed sensitivity to action of these regulatory polypeptides.     

Changes in the blood immunological indices of newborn infants as affected by T-activin in vitro

T-activin, introduced into the culture of mononuclear cells obtained from the blood of healthy newborn infants, does not induce any essential changes in the levels of E-, Ea- and EAC-rosette-forming cells. An overwhelming majority of healthy infants has shown a decrease in the functional activity of lymphocytes in the blast transformation test in response to the optimal dose of ConA and an increase in their functional activity in response to the suboptimal dose of this mitogen. After stimulation with phytohemagglutinin, both the increase of the stimulation index and its decrease have been observed in an equal number of cases. The introduction of the preparation into the culture of mononuclear blood cells isolated from newborn infants with sepsis leads to a considerable increase in the detection rate of Ea-rosette-forming cells with a tendency to an increase in that of E- and EAC-rosette-forming cells. The final values of the stimulation indexes, no matter what the mitogens used, are in conformity with the values characteristic of the normal parameters for healthy newborns, due to a specific pattern of changes in the T-lymphocyte functional activity in the blast-transformation test.     

Metabolic state of liver mitochondria and lymphocytes after T-activin administration under condition of hypothermia

After 10 days of swimming (10 min per day, water temperature +20 degrees C) the oxygen consumption in rat liver mitochondria increased via the external pathway of NADH oxidation from 3.6 +/- 0.3 to 4.4 +/- 0,2 nmoles O2 x min-1 x mg-1 protein; when the rats were simultaneously injected with an endogenous immunomodulator T-activin (5 micrograms/100 g body weight) daily, this rate increased up to 6.5 +/- 0.6 nmoles O2 x min-1 x mg-1 protein. In the control group, the uncoupled respiration rate is also higher, while the ascorbate+ +TMPD oxidation rate is lower than in the cold- and cold + T-activin-treated groups. The metabolic states of lymphocyte mitochondria did not differ in the three experimental groups. The respiration rates and delta psi m (monitored by diS-C3-(5) fluorescence) of lymphocyte mitochondria in these three groups were also identical.