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The Effect Of Directive Differentiation Of Mice DC On The Induction Of Th Cell Subtype Under The Stimulation Of MBP

Posted on:2004-06-06Degree:MasterType:Thesis
Country:ChinaCandidate:F X SongFull Text:PDF
GTID:2144360122998050Subject:Neurology
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The Effect of Directive Differentiation of Mice DC on the Induction of Th Cell Subtype under the Stimulation of MBPThe demyelinating disease of the central nervous system (CNS) such as multiple sclerosis (MS) is the common disease of nervous system, it is a kind of disease which usually takes place in the young age with high incidence and high disability-causing rate and usually with a progressive manifestation whose pathogenesis is still unknown. It is regarded as a disease with multiple etiological factors and virus infection maybe play a role during the disease, and its onset may relate to the dysfunction of immune system of allergic reaction under the effect of environment and heredity. The pathogenesis of the demyelinating disease of CNS resembles other autoimmune disease whose process is relevant to autoantigens, activation of unspecific T cell and the inflammation reaction induced by T cell especially CD4+ T-helper cell one (Th1). Myelin basic protein (MBP) is not only the important element of nervous myelin, but also the major antigen of the demyelinating disease of CNS. The' experimental allergic encephalomvelitis (EAE) of animal induced by MBP which is similar with the human demyelinating disease of CNS in clinical manifestation, immunopathology and immunochemistry is therefore a typical animal model to study the demyelinating disease of CNS. Dendritic cell (DC) which act as the strongest antigen presenting cell (APC) in the body play an important role in demyelinating disease of CNS. Relating study showed that DC had an important effect in the induction of EAE primary immune reaction, induction of immune tolerance and the differentiation from T cell to Thl or Th2. DC has plastic function, controlling in vitro culture environment can change the function of DC or make its directive differentiation, so the differentiation of Thl and Th2 ,whether it is existing or has existed can been changed. So the study to the onset of EAE also the change and effect of DC during the disease has been becoming the focus of research. Some foreign scholars have noticed the effect of DC during the process of demyelinating disease of CNS, and no relating report have been published domestically.This experiment made use of the in vitro cell culture method to separate DC from the spleen of BALB/c mice susceptible to EAE and co-cultured them with MBP, IL-4 and IL-3 of recombinant mice respectively, then co-cultured DC got from above different conditions with mononuclear cells which had discarded DC. Through the detection of the supernatantcontent of IL-4 and IFN- y , the observation of the effect of different subtype of DC on the differentiation of Th cell into Thl and Th2 have been made. It can give an experimental foundation that by the control to DC 1/DC2 to modulate the answer balance of Th1/Th2 and the dominant response type of Thl and Th2 therefore to block the cellular immunity mediated by Thl to promote the recovery of demyelinating disease of CNS or reducing the relapse of it.The result of this experiment are as follows:1 , Co-culture of IL-3, GM-CSF of recombinant mice with precursor DC of BALB/c mice susceptible to EAE under the stimulation of MBP showed an increase in DC2 differentiation from precursor DC. then co-cultured DC got from above condition with mononuclear cells which had discarded DC. the IL-4 level of supernatant was obviously higher than that of control group, while the content of IFN- v had no significant difference with that of control group. The average content of IL-4 of study group was 10.9457 + 2.9180,the average content of that of control group was 9.2057+ 1.3187,it showed a significant difference between above two groups(t=2.10,P<0.05). The average content of IFN- Y of study group was 27.8422 + 3.5225, the average content of that of control group was 28.6565 + 4.4724, it showed no significant difference between above two groups(T=2.10,p>0.5).2,Co-culture of IL-4, GM-CSF of recombinant mice with precursor DC of BALB/c mice susceptible to EAE under the stimulation of MBP showed an incre...
Keywords/Search Tags:myelin basic protein, dendritic cell, IL-4, IL-3, experimental allergic encephalomyelitis, Th1/Th2 cell
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