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Induction Of Allergen-specific Immune Tolerance By Dendritic Cell Co-transfected With FasL And Der PⅡ Genes In Mice Sensitized/challenged By HDM Allergen

Posted on:2007-05-03Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y WangFull Text:PDF
GTID:1104360185970481Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Asthma is a chronic inflammatory disorder of the airway caused by many inflammatory cells. Th1/Th2 paradigm is known as the main pathogenesis of asthma. Excess activation of Th2 cells evokes Th2 immune response, and it causes elevated Th2 cytokines. Th2 cytokines such as IL-4, IL-5 and IL-13 play a pivotal role on the onset and maintenance of airway allergic inflammation in asthma. More recently, it has been found that Th1/Th2 paradigm can not explain the immune dysfunction of asthma completely. Because of immune tolerance to harmless allergen, harmless allergens do not lead to excess activation of T cells in healthy person. But in asthmatic patients, harmless allergens induce excess activation and proliferation of T cells, and make T cells differentiate into Th2 cells. Therefore, defect of immune tolerance may be an important mechanism for asthma. Dendritic cell(DC) is the most powerful of antigen presenting cell(APC) in the present.DC controls immune response and determines tolerance or immunity to encountered allergen. Therefore, DC plays dual task of initiating immune response and maintaining immune tolerance. T cells apoptosis mediated by Fas/FasL is a major mechanism for peripheral immune tolerance. As an attempt to selectively deplete T cells that recognize a given antigen, cDNA encoding a death ligand FasL was transfected into DC or other APC, termed"killer"DC or APC. Many reports showed that antigen-specific immunosuppression is inducible using FasL-transduced killer APC.In the present study, DC was co-transfected with FasL cDNA and Der pII cDNA (house dust mite allergen), named"FasL-Der pII-DC", and induction of immune tolerance by FasL-Der pII-DC in mice sensitized/challenged by house mite dust extract(HDM) was investigated. In addition, we compared FasL-Der pII-DC with FasLcDNA-transduced DC(FasL-DC) or Der pIIcDNA-transduced DC(Der pII-DC) in inducing immune tolerance.Methods:1. The full length cDNA of mouse FasL(mFasL) was cloned by RT-PCR from...
Keywords/Search Tags:allergy, immune tolerance, Fas ligand, house dust mite, dendritic cell
PDF Full Text Request
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