Contribution of regulatory T cells to alleviation of experimental allergic asthma after specific immunotherapy.

BACKGROUND: Allergen-specific immunotherapy (SIT) has been used since 1911, yet its mechanism of action remains to be elucidated. There is evidence indicating that CD4(+)FOXP3(+) regulatory T cells (Treg cells) are induced during SIT in allergic patients. However, the contribution of these cells to SIT has not been evaluated in vivo. OBJECTIVE: To evaluate the in vivo contribution of (i) CD4(+) CD25(+) T cells during SIT and of (ii) SIT-generated inducible FOXP3(+) Treg cells during allergen exposure to SIT-mediated suppression of asthmatic manifestations. METHODS: We used a mouse model of SIT based on the classical OVA-driven experimental asthma. Treg cells were quantified by flow cytometry 24 and 96 h post SIT treatment. We depleted CD4(+) CD25(+) T cells prior to SIT, and CD4(+)FOXP3(+) T cells prior to allergen challenges to study their contribution to the suppression of allergic manifestations by SIT treatment. RESULTS: Our data show that depletion of CD4(+)CD25(+) T cells at the time of SIT treatment reverses the suppression of airway hyperresponsiveness (AHR), but not of airway eosinophilia and specific IgE levels in serum. Interestingly, the number of CD4(+)CD25(+)FOXP3(+) T cells is transiently increased after SIT in the spleen and blood, suggesting the generation of inducible and presumably allergen-specific Treg cells during treatment. Depletion of CD4(+)FOXP3(+) Treg cells after SIT treatment partially reverses the SIT-induced suppression of airway eosinophilia, but not of AHR and serum levels of specific IgE. CONCLUSION AND CLINICAL RELEVANCE: We conclude that SIT-mediated tolerance induction towards AHR requires CD4(+)CD25(+) T cells at the time of allergen injections. In addition, SIT generates CD4(+)CD25(+)FOXP3(+) T cells that contribute to the suppression of airway eosinophilia upon allergen challenges. Therefore, enhancing Treg cell number or their activity during and after SIT could be of clinical relevance to improve the therapeutic effects of SIT.

[RNA synthesis in rat brain during pharmacological modification of norepinephrine metabolism]. / Sintez RNK v golovnom mozge krys pri farmakologischeskikh vozdeistviiakh na obmen noradrenalina.

Norepinephrine metabolism and nuclear RNA (nRNA) synthesis in the rat brain are found to be conjugated. Under the effect of preparations inducing a disturbance in the norepinephrine (sodium diethyldithiocarbamate and reserpine) its content in the brain tissue lowers and the nRNA synthesis intensity decreases. Accumulation on total resources of norepinephrine in the brain under the effect of ipraside or its synaptic form (melipramine, Lu-5) intensifies the nRNA synthesis.

[Catecholamine storage in schizophrenia]. / Deponirovanie katekholaminov pri shizofrenii.

After administration of isadrine excretion of noradrenaline was increased in schizophrenic patients with symptoms of depression or anxiety. This phenomenon was not observed in healthy persons and in patients with circular depression. Data on liberation of noradrenaline by other amines in schizophrenia and displacement of noradrenaline in schizophrenia by isadrine, which does not accumulate in normal storage sites, suggest that storage of noradrenaline is impaired in schizophrenia.

[Experimental study of the emotiontropic effect of lithium: ambivalent dose-dependent effect in "reserpine depression" and preventive anti-stress effect]. / Eksperimental'noe issledovanie emotsiotropnogo deistviia litiia: ambivalentnoe doze-zavisimoe vliianie pri "rezerpinovoi depressii" i preventivnyi antistressornyi éffekt.

Experiments on male-rats with a chronic administration of lithium show that it exerts a dose-dependence ambivalent action on the biochemical and behavioural characterisics of "reseprine depressions". In this way changes in the catecholeamine excretion and disturbances of conditioned reactions of advoidance are prevented (in dosages 10 mg/kg , and increasing them to 50 mg/kg). An opposite influence of different doses of lithium was also seen in a study of the hypothalamic resources of noradrenalin in the remote period of an after action of reserpine. The use of lithium exerts an expressed preventive effect in experimental emotional stress, preventing the development of suprarenal reactions and disorders of conditioned reflexes of avoidance. The authors discuss some neurochemical mechanisms of ambivalent and emotiotropic effect of lithium and the exedience of an enlargement of its prophylactic use.

[Changes in the noradrenaline level and synthesis of nuclear RNA in the brain of rats with disturbances of the emotions and conditioned-defense behavior]. / Izmeneniia soderzhaniia noradrenalina i sintez iadernoi RNK v golovnom mozge krys pri narushenii émotsional'nogo i uslovno-oboronitel'nogo povedeniia

Brain noradrenaline (Na) exhaustion in reserpine-, disulfiram-or diethyldithio carbamate-treated rats was followed by a fall of the nRNA synthesis, emotional and conditioned behaviour disturbances. In accumulation of cerebral NA (ipraside and imipramine injections) there is an increase in the rate of synthesis, of the nuclear RNA. Prevention of the exhausting effect of reserpine by a preliminary injection of ipraside also prevented disturbances of the nuclear RNA synthesis.

[Catecholamines in the pathochemical structure of depressive conditions (according to material from a biological study)]. / Katekholaminy i patokhimicheskoi strukture depressivnyky sostoianii (po materialam biologicheskogo issledovaniia)

By a combination of biochemical and pharmacodynamical analyses the author conducted a differentiated study of the role of separate neurohormones (adrenalin, noradrenalin, dopamine, serotonine) and their interconnection with other regulating systems (corticosteroids, nucleic acids) in the neurochemical structure of experimental models in depressive behaviour (reserpine depressions, depressions due to inhibitors of dopamine-beta-oxydase). In the aspect of the author's concept concerning reciprocity of relationships between the central and peripheral catecholamine mechanisms on the basis of the obtained experimental data, their comparison with the previous clinico-biochemical investigations and literary data is considered to be the pathochemical basis of depression. This is considered to be a multicomponent structure of pathologically fixed changes of the central noradrenergic activity, relationships in the catecholaminergic system (hypothalamus--medullau substance of the adrenal glands) and processes of reswitching catecholamine influences on the state of other neurochemical regulatory systems.