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Thymus and self-unresponsiveness : Cellular and molecular basis for the generation of autoimmunity in neonatally thymectomized mice
http://hdl.handle.net/10191/5439
http://hdl.handle.net/10191/54394e5994d1-94bf-4946-8e10-4d59d17d0e55
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
本文 (10.5 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2008-04-08 | |||||
| タイトル | ||||||
| タイトル | Thymus and self-unresponsiveness : Cellular and molecular basis for the generation of autoimmunity in neonatally thymectomized mice | |||||
| タイトル | ||||||
| タイトル | Thymus and self-unresponsiveness : Cellular and molecular basis for the generation of autoimmunity in neonatally thymectomized mice | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | autoimmune gastritis | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | eosinophil | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | thymectomy | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | 自己免疫性胃炎 | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | 好酸球 | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | 胸腺摘出手術 | |||||
| 資源タイプ | ||||||
| 資源 | http://purl.org/coar/resource_type/c_46ec | |||||
| タイプ | thesis | |||||
| その他のタイトル | ||||||
| その他のタイトル | 胸腺と自己認識 : 新生仔胸腺摘出によって誘導される自己組織破壊反応の細胞分子基盤について | |||||
| 著者 |
Fujii, Masato
× Fujii, Masato |
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| 著者別名 | ||||||
| 識別子Scheme | WEKO | |||||
| 識別子 | 49261 | |||||
| 姓名 | 藤井, 庄人 | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Neonatal thymectomy induces autoimmune gastritis in relatively higher incidence in BALB/c mice, whereas DBA/2 mice are quite resistant. The incidence of AIG has been thought to be related with activation of Vβ6^+ T cells reacting Minor lymphocyte stimulating (Mls)-la antigens because the susceptible BALB/c mouse is Mls-la-negative, while DBA/2 mouse is Mls-la-positive. Supporting this idea, a proportion of Vβ6^+, but not of Vβ8^+, T cells increased in AIG NTx BALB/c mice and these mice were up-regulated in IFN-γ production from young. Conversely, the deletion of Vβ6^+ T cells in BALB/c mice by transplantation of DBA/2 bone marrow cells as neonate resulted in decreasing the incidence of AIG. However, it was surprising that these chimeric mice lacking Vβ6^+ T cells possessed autoreactive T cells which could transfer the disease in nude mice. Moreover, Vβ6^+ T cells which deleted by transplantation of bone marrow cells from Mls-la^+ mice possessing BALB/c genetic background could not make BALB/c mice resistant. Thus, the presence or absence of Mls-la antigens would not be involved in the initiation of AIG. On the other hand, IFN-γ-producing CD4^+ T cells of NTx BALB/c mice were decreased by transplanted with DBA/2 bone marrow cells as neonate: NTx DBA/2-chimeric BALB/c mice were thought to be under the anti-inflammatory state. Indeed, DBA/2-originated myeloid cells showed increased IL-10-production. These results indicate that the controlling mechanism for the AIG incidence is on the secreted quantity of anti-inflammatory cytokine from myeloid cells under the genetic control. A unique pathological feature of murine autoimmune gastritis (AIG) in mice is its pronounced mucosal hypertrophy, which is different from human type-A chronic atrophic gastritis with pernicious anemia. The aim of this study was to clarify the mechanism of gastric hypertrophy in murine AIG, especially in relation to inflammatory cells infiltrating in the gastric mucosa. Neonatally thymectomized (NTx) BALB/c and (BALB/c×DBA/2) F1 mice with gastritis were examined histologically and serologically. The T-helper (Th1/Th2) immune balance in the spleen was evaluated by intracellular cytokine staining for interferon-γ and flow-cytometric beads array for several cytokines. Additionally, AIG NTx BALB/c mice were orally administered with an H_2-blocker to decrease eosinophils. Obtained results are as follows: AIG NTx BALB/c mice exhibited gastritis without stomach hypertrophy at two months old, and developed gastritis with mucous gland hypertrophy accompanied with eosinophil infiltration at six months old. In contrast, AIG NTx (BALB/c×DBA/2) F1 mice displayed gastritis with neither stomach hypertrophy nor eosinophil infiltration even at the age of six months. Upregulation of IL-4 and GM-CSF in the spleen was observed in BALB/c mice but not in (BALB/c×DBA/2) F1 mice. Additionally, some AIG NTx BALB/c mice did not show gastric hypertrophy or eosinophil infiltration due to the administration of an H_2-blocker. As conclusions, there are two different pathological phenotypes of murine autoimmune gastritis: chronic gastritis and hypertrophic gastritis in AIG NTx BALB/c mice. Furthermore, eosinophil infiltration and Th2 immune response might play a key role in the phenotypic shift from chronic gastritis into hypertrophic gastritis in AIG NTx BALB/c mice. | |||||
| 書誌情報 | p. 1-71, 発行日 2007-03-22 | |||||
| 出版者 | ||||||
| 出版者 | 新潟大学大学院自然科学研究科 | |||||
| 著者版フラグ | ||||||
| 値 | author | |||||
| 学位名 | ||||||
| 学位名 | 博士（理学） | |||||
| 学位授与機関 | ||||||
| 学位授与機関名 | 新潟大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2007-03-22 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 13101甲第2838号 | |||||
| 学位記番号 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 新大院博（理）甲第276号 | |||||
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Cite as
Fujii, Masato, 2007, Thymus and self-unresponsiveness : Cellular and molecular basis for the generation of autoimmunity in neonatally thymectomized mice: 新潟大学大学院自然科学研究科, p. 1–71.
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