Immunological responses against hepatitis B virus in human peripheral blood mononuclear cell-engrafted mice
| Autor: | Akira Nishio, Tomohide Tatsumi, Takeshi Takahashi, Yoshiki Onishi, Satoshi Aono, Takahiro Kodama, Seiichi Tawara, Ryotaro Sakamori, Minoru Shigekawa, Keisuke Fukutomi, Teppei Yoshioka, Hiroshi Suemizu, Tetsuo Takehara, Tasuku Nakabori, Hayato Hikita |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Hepatitis B virus T cell T-Lymphocytes Biophysics Mice SCID medicine.disease_cause Biochemistry Peripheral blood mononuclear cell law.invention 03 medical and health sciences Mice 0302 clinical medicine Immune system law MHC class I Medicine Animals Humans Molecular Biology Mice Knockout biology business.industry Cell Biology Hep G2 Cells Vaccination Disease Models Animal 030104 developmental biology medicine.anatomical_structure Humanized mouse Immunology Recombinant DNA biology.protein Leukocytes Mononuclear business 030215 immunology |
| Zdroj: | Biochemical and biophysical research communications. 503(3) |
| ISSN: | 1090-2104 |
| Popis: | It is well known that immune-mediated virus elimination is necessary for the treatment of HBV infection. Reconstitution of human immune cells in liver chimeric mice is warranted to understand the immunopathogenesis of HBV infection. Here, we report a new immunologically humanized mouse model with a human immune system via reconstitution of immunodeficient NOG-Iaβ/β2 m double KO mice, which are NOG mice that are deficient in both MHC class I and II (DKO-NOG mice), with human HLA-A2-positive peripheral blood mononuclear cells (PBMCs). After injection of PBMCs, the xenogeneic graft-versus-host disease observed in PBMC-engrafted NOG mice was prevented in PBMC-engrafted DKO-NOG mice. Liver damage was reduced, and the survival time was prolonged in human PBMC-engrafted DKO-NOG mice compared to those in the NOG mice. The expression levels of PD-1 and Tim-3 on human T cells from PBMC-engrafted DKO-NOG mice were lower than those from NOG mice. By induction of HBV-specific T cell responses, such as vaccination with HBc-derived, peptide-pulsed DCs, hydrodynamic injection of HBV vector and intrasplenic injection of HepG2.2.15, the number of HBc-derived, peptide-specific CTLs increased in PBMC-engrafted DKO-NOG mice. Moreover, the recombinant HBV vaccine resulted in the production of hepatitis B surface antibody in 50% of the vaccinated mice. The induction of HBV-specific immune responses could be established in the immunologically humanized mice. |
| Databáze: | OpenAIRE |
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