論文 - 詳細
| RRC ID | 44291 |
|---|---|
| 著者 | Ishikawa Y, Usui T, Shiomi A, Shimizu M, Murakami K, Mimori T. |
| タイトル | Functional engraftment of human peripheral T and B cells and sustained production of autoantibodies in NOD/LtSzscid/IL-2Rγ(-/-) mice. |
| ジャーナル | Eur J Immunol |
| Abstract |
NOD/LtSzscid/IL-2Rγ(-/-) (NSG) mice have advantages in establishing humanized mouse models. However, transferring human PBMCs into these mice often causes lethal GVH disease. In this study, we discovered an improved method for the engraftment of normal or pathological human PBMCs into NSG mice and examined the subsequent induction of specific immune responses. We sequentially transferred human CD4+ memory T (Tm) and B cells obtained from PBMCs of healthy adults or patients with autoimmune diseases into NSG mice. Removing naïve CD4+ T cells from the transferred PBMCs allowed successful engraftment without lethal GVH disease. The transferred Tm cells were found to reside mainly in the spleen and the lymphoid nodules, where they expressed MHC class II molecules and produced cytokines, including IL-21. Surprisingly, the transferred B cells were also well maintained in the lymphoid organs, underwent de novo class-switch recombination, and secreted all isotypes of human Igs at significant levels. Moreover, transferring patient-derived Tm and B cells resulted in sustained production of IgM-rheumatoid factor and antiaminoacyl transfer RNA synthetase Abs in these mice. These results suggest that transfer of Tm and B cells derived from human PBMCs into NSG mice could be a useful method for the study of human autoimmune mechanisms. |
| 巻・号 | 44(11) |
| ページ | 3453-63 |
| 公開日 | 2014-11-1 |
| DOI | 10.1002/eji.201444729 |
| PMID | 25154613 |
| MeSH | Animals Autoantibodies / biosynthesis* Autoantibodies / immunology Autoimmunity / immunology B-Lymphocytes / cytology B-Lymphocytes / immunology B-Lymphocytes / transplantation* CD4-Positive T-Lymphocytes / immunology CD4-Positive T-Lymphocytes / transplantation* Cells, Cultured Graft vs Host Disease / immunology Graft vs Host Disease / prevention & control Humans Immunoglobulin Class Switching / genetics Immunoglobulin Class Switching / immunology Immunoglobulin G / blood Immunoglobulin G / immunology Immunoglobulin M / blood Immunoglobulin M / immunology Interleukin-21 Interleukins / biosynthesis Leukocyte Common Antigens / biosynthesis Mice Mice, Inbred NOD Mice, Knockout Mice, SCID Monocytes / immunology Monocytes / transplantation Transplantation, Heterologous / methods* |
| IF | 2.989 |
| 引用数 | 9 |
| WOS 分野 | MICROBIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Jurkat |