Reproduction of virus-specific immunodeficiency in humanized mice

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670198
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: National Research Institute for Child Health and Development
• Principal Investigator: FUJIWARA Shigeyoshi 独立行政法人国立成育医療研究センター, その他部局等, その他 (30173488)
• Co-Investigator(Renkei-kenkyūsha): IMADOME Ken-ichi 国立成育医療研究センター, 母児感染研究部, 室長 (70392488) ; MATSUDA Go 国立成育医療研究センター, 母児感染研究部, 研究員 (60392130) ; KANEGANE Hirokazu 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (00293324)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: EBウイルス / ヒト化マウス / XIAP欠損症 / 免疫不全症 / サイトカイン

Outline of Final Research Achievements

To reproduce EBV-related immunodeficiency in humanized mice, hematopoietic stem cells were isolated from a patient with XIAP deficiency and transplanted to four NOG mice. Three of the four mice showed signs of reconstitution with human immune system components; 0.3-20.4% of PBMC was positive with human-specific anti-CD45 antibody. Two of the three mice were inoculated with EBV and EBV DNA (up to 8×10E+3 copies/μg DNA) was detected in the peripheral blood 6-10 weeks post inoculation. The percentage of CD8+ T cells among peripheral blood lymphocytes increased drastically to ~80% in these mice. These results indicated that humanized mice could be prepared with stem cells isolated from a patient with XIAP deficiency, and EBV can infect these mice and induce CD8+ T cell responses. Peripheral blood levels of human cytokines are currently evaluated to see if hypercytokinemia, characteristic to EBV infection in patients with XIAP deficiency, is reproduced in these mice.

Free Research Field

ウイルス学