RESUMEN
BACKGROUND: At the development of graft versus host disease in genetically homogeneous population of (C57BI/6 x DBA/2) Fl mice two clinical phenotypes of SLE-like disease were revealed: lupus+ (immune complex glomerulonephritis and hemnolytic anemia) and lupus - (hemolytic anemia). The GvHD phenotypic heterogeneity is determined by the Th2-polarization: Th2 lymphocyte predominant activity, leads to the lupus+development, or prevalence activity of Th1 cells, leads to the lupus- development. OBJECTIVE: Our aim was to evaluate the possibility of using an experimental model of autoimmnune disease for studying and testing of epigenetic modifications, shifting Th1/Th2 balance in vivo. METHODS: Chronic GVHD was induced in B6D2F1 mice by the transplantation of 130x10(6) parental DBA/2 splenocytes. Anti-ds-DNA, total IgG and IgGI, IgG2a Abs were measured by ELISA. RESULTS: Six- to 8-week-old female DBA/2 and B6D2F1 mice were obtained from Biological Research Laboratory (Novosibirsk). It was established that regular moderate physical activity (unladed swimming) shifted Th1/Th2 balance towards Th1. This leads to a decrease in a population of recipients the lupus+ mice from 57 to 26% (p <0,001) with significantly reduced hypergammaglobulinemia (IgG from 2,8 to 2,0 mg/ml; p <0,047) and DNA antibodies titer from 0,18 to 0,12 OD (p =0,05). Administration of epigenetic modificator bisphenol A at low doses, which mimicking estrogen effects, enhances the proportion of lupus+ mice in experimental groups from 33 to 64% (p <0,001) and impairs their clinical status by the increasing the urine protein level from 2.8 to 4,2 mg/ml (p <0,001) in animals. CONCLUSION: Th1/Th2 - balance presumably is determined by the immune system epigenetic modification in experimental mice, formed on the previous stages of ontogeny and defines the direction of immune processes development in individual animal.
Asunto(s)
Enfermedades Autoinmunes/genética , Autoinmunidad/genética , Epigenómica/métodos , Enfermedad Injerto contra Huésped/genética , Linfocitos T/inmunología , Animales , Enfermedades Autoinmunes/inmunología , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Enfermedad Injerto contra Huésped/inmunología , Inmunoglobulinas/inmunología , Túbulos Renales/inmunología , Túbulos Renales/metabolismo , Túbulos Renales/patología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Bazo/inmunología , Bazo/trasplanteRESUMEN
Additional dose of the antigen at the end of the log phase of developing IgM response to T-dependent antigen leads to a drastic increase in the counts of IgM and IgG antibody-producing cells in the spleens of experimental animals. The effect is dose-dependent and more pronounced after the first immunization with the antigen in the suboptimal dose. Elimination of proliferating antibody producers has an ambiguous effect on IgM and IgG antibody production in the spleen: it limits the increase in the count of IgM-producing cells, but does not abolish the stimulation of IgG response. It seems that the increase in the count of IgG producers is not linked with simultaneous active proliferation of IgG producing cell precursors.
Asunto(s)
Células Productoras de Anticuerpos/inmunología , Inmunidad Humoral/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Bazo/inmunología , Animales , Relación Dosis-Respuesta a Droga , Eritrocitos/inmunología , Femenino , Hidroxiurea , Ratones , Ratones Endogámicos C57BL , Ovinos , Bazo/citologíaRESUMEN
The process of formation of multiple spindles in mononucleate pollen mother cells during meiosis in general wide hybrids F1 and haploids is described. It is assumed that the abnormality may be caused by aberration of a special process at late prometaphase providing for the spindle consolidation.