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Human Interleukin-15 And Interleukin-12 Respectively Improve Engraftment Of Human Lymphocytes In NOD-SCID Mice And Immune Responses Of HBsAg Vaccine In HuPBL/NOD-SCID Mice

Posted on:2007-12-31Degree:DoctorType:Dissertation
Country:ChinaCandidate:A Y SunFull Text:PDF
GTID:1104360185451501Subject:Cell biology
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During past decades, several models have been reported and improved the studies involving the pathogenesis of human diseases and the drug discovery. Because of the distinction between human immune system and animal's, establishment of human-mouse chimera with human immune systems will be extremely helpful for the exploration of human immune functions and for evaluating the vaccine efficiency using animal models. In recent years, several human/SCID chimera models have been reported, such as implantation of human embryo's thymus, fetus liver or fetus bone marrow, even human PBL to SCID mice, i.e. SCID-hu Thy/Liv, SCID/huBone, and SCID/HuPBL, respectively. In huPBL/SCID model, all human T cells and B cells function normally, and the model can be used to examine human immunoglobulin production.HuPBL/SCID mice have successfully been employed in various studies on human immune function. However, at the early stage of human PBL engraftment, only a small fraction of transferred human cells (0.1% of the original grafted) can be detected in the HuPBL/SCID chimera. Owing to the deficiency, the model has been narrowed for wide application and could not be employed in analysis of antigen-specific cellular immune responses. Although various strategies have been modified to further improve the efficiency of huPBL engraftment into HuPBL-SCID mice, e.g. by increasing the transferred cell number, destroying the recipient mice via low-dose irradiation or eliminating mouse natural killer (NK) cells by anti-asialo-GM1, or adopting both irradiation and anti-asialo-GM1 treatment. In the other hand, several biological agents as a stimulant of human hematopoietic cells have been examined for promoting the transferred lymphocytes into HuPBL-SCID mice, including IL-6, IL-4, growth hormone and chemokine. These modifications have showed only marginally effects if considered...
Keywords/Search Tags:NOD-SCID mice, human/mouse chimera, interleukin-15, lymphocytes, trafficking, engraftment, interleukin-12, HBsAg vaccine, immunization
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