Importance of hepatic lymphocytes on innate immunity

肝淋巴细胞对先天免疫的重要性

• 批准号: 14370162
• 负责人: ABO Toru
• 金额: $ 8.58万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14370162/
• 关键词: autoimmune disease; extrathymic T cells; B-1 cell; human liver lymphocyte; B-2 cell; liver transplantation; NZB; WF_1 mice; malaria

Malarial parasites are intracellular pathogens and therefore invade erythrocytes and hepatocytes. In this respect, conventional T and B cells could not function against the parasites. Inversely, extrathymic T cells and B-1 cells attack such parasites by their autoreactivity and autoantibodies. These evidences were produced in both murine and human studies. We also found that erythropoiesis was induced in the liver of mice after malarial infection. It is speculated that fresh erythrocytes produced in the liver might be an important target for the parasites. TAP-1(-/-) mice with missing self were also used in this study and extrathymic T cells were abundant in these mice. Innate immunity mediated by extrathymic T cells is found to be importance to eliminate missing self. A similar phenomenon was also seen in mice with stress and in mice with amyloidosis. Granulocytes are also important in parallel with extrathymic T cells and B-1 cells. In 2004, anti-erythropoietin antibody was found to cure malaria when injected into mice with malaria. In 2005 final year, the activation of NKT cells by α-GalCer induced hepatic failure. This result indicated that overactivation of NKT cells is able to induce tissue damage. NK1.1-TCR^<int> cells are also found to be a major lymphocyte subset in malarial infection.

疟疾寄生虫是细胞内病原体，因此侵入红细胞和肝细胞。在这方面，传统的 T 细胞和 B 细胞无法对抗寄生虫。相反，胸腺外 T 细胞和 B-1 细胞通过自身反应性和自身抗体攻击此类寄生虫。这些证据是在小鼠和人类研究中得出的。我们还发现，感染疟疾的小鼠肝脏中诱导了红细胞生成。据推测，肝脏中产生的新鲜红细胞可能是寄生虫的重要目标。本研究还使用了自我缺失的TAP-1(-/-)小鼠，这些小鼠体内胸腺外T细胞丰富。人们发现，由胸腺外 T 细胞介导的先天免疫对于消除缺失的自我非常重要。在承受压力的小鼠和患有淀粉样变性的小鼠中也观察到类似的现象。粒细胞与胸腺外 T 细胞和 B-1 细胞同样重要。 2004年，人们发现将抗促红细胞生成素抗体注射到患疟疾的小鼠体内可以治愈疟疾。 2005年的最后一年，α-GalCer激活NKT细胞导致肝衰竭。这一结果表明NKT细胞的过度激活能够引起组织损伤。还发现NK1.1-TCR^<int>细胞是疟疾感染中的主要淋巴细胞亚群。

项目成果

Association of CD8^+ natural killer T cells in the liver with neonatal tolerance phenomenon.

肝脏中 CD8^ 自然杀伤 T 细胞与新生儿耐受现象的关联。

• 发表时间: 2002
• 期刊: Transplantation 73
• 作者: Kawamura;H. et al.
• 通讯作者: H. et al.

Reasons why DBA/2 mice are resistant to malarial infection : expansion of CD3^<int>B220^+γδT cells with double-negative CD4^-8^- phenotype in the liver.

DBA/2小鼠对疟疾感染具有抵抗力的原因：具有双阴性CD4^-8^-表型的CD3^<int>B220^+γδT细胞在肝脏中的扩增。

• 发表时间: 2006
• 期刊: Immunology 117
• 作者: Bakir;H.Y.et al.
• 通讯作者: H.Y.et al.

Kato, T. et al.: "Involvement of natural killer T cells and granulocytes in the inflammation induced by partial hepatectomy"J.Hepatol.. 40. 285-290 (2004)

Kato, T. 等人：“自然杀伤 T 细胞和粒细胞参与部分肝切除术诱导的炎症”J. Hepatol.. 40. 285-290 (2004)

Granulocytic activation and reciprocal immunosuppression induced by dehydration : relationship with renal failure

脱水引起的粒细胞活化和相互免疫抑制：与肾衰竭的关系

• 发表时间: 2004
• 期刊: Biomedical Research 25(4)
• 作者: Changchun Li;Nakako Izumi;Kazuto Ebe;Masahito Tsuchida
• 通讯作者: Masahito Tsuchida

Tissue‐specific expansion of NKT and CD5+B cells at the onset of autoimmune disease in (NZB×NZW)F1 mice

(NZB×NZW)F1 小鼠自身免疫性疾病发作时 NKT 和 CD5+B 细胞的组织特异性扩增

• 发表时间: 2002
• 期刊: European Journal of Immunology
• 影响因子: 5.4
• 作者: S. Morshed;K. Mannoor;R. Halder;H. Kawamura;M. Bannai;H. Sekikawa;Hisami Watanabe;T. Abo
• 通讯作者: T. Abo