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論文(リポジトリ) |
論文(リポジトリ)
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宮路, 智香子
概要:
Recent studies demonstrated that murine liver contained extrathymically differentiated T cells. These cells express inte
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rmediate (int) level of TCR (CD3) and IL-2Rβ chain. However, it has been unknown about the development of these int TCR cells without requirement of thymus. Here, we investigated how the int TCR cells were differentiated and proliferated. The int TCR cells but not the other peripheral T cells responded to exogenous IL-7 which supported TCR cell differentiation in thymus. Similar to the bone marrow (BM), the liver contained hematopoietic stem cells (c-kit^+Lin^-) which enabled to reconstitute T, B, macrophage and myeloid cells in irradiated SCID mice. In vitro, the hematopoietic stem cells in the liver did not differentiate into the int TCR cells either in the presence of fetal thymus or thymic stromal cells. However liver-derived stromal cells which could produce IL-7 and other cytokines, supported int TCR cell differentiation. On the other hand, those in BM did not develop the int TCR cells in any condition. Taken together, the int TCR cells in the liver are supposed to be developed in situ from the hematopoietic stem cells in the liver in association with some cytokines like IL-7.
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| 2.
論文(リポジトリ) |
論文(リポジトリ)
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羽生, 忠正
概要:
To study joint destruction and osteoporosis in patients with rheumatoid arthritis (RA), we investigated bone loss using
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histomorphometric analysis. We also examined the property of colony forming unit-fibroblastic (CFU-F) isolated from tibial bone marrow in rats with collagen-induced arthritis (CIA) and iliac bone marrow in human. Our findings showed decreases of parameters of bone formation and of the number of alkaline phosphatase-positive CFU-F during onset of arthritis. We speculated that reduced bone formation was the predominant mechanism of bone loss in the pathogenesis of RA. We also demonstrated that the lymphocytes in the joints of CIA comprised resident T cells that are extrathymically generated in situ. In vivo treatment with various monoclonal antibody, these γδT cells and CD 8 _<αα>^+ cells were associated with suppression of the disease, especially after its onset. On the other hand, in patients with RA, CD57^+T cells levels were elevated, especially high in joints and its adjacent bone marrow. CD57^+T cells contained higher proportions of CD ^4-^8- cells and γδT cells than CD57^-T cells. We suggested that CD57^+T cells with NK cell marker probably were a counterpart of extrathymic T cells in human and had unique immuno-suppressive functions. In rats with CIA, great increase in number of granulocytes were also observed before the onset of arthritis. From these results, we are performing the evaluation of these treatment which makes it possible to decrease the granulocytes or to increase the CD57^+T cells using previous analysis system of bone formation.
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| 3.
論文(リポジトリ) |
論文(リポジトリ)
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川村, 俊彦
概要:
肝臓は,末梢のリンパ臓器とは大きく異なるリンパ球分布を示し,消化・代謝臓器としてのみならず,免疫臓器として注目されている.肝臓に多くみられるリンパ球としては,NKT細胞,NK細胞,胸腺外分化T細胞,γδT細胞などが挙げられるが,これら肝臓特
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異的なリンパ球は,肝炎などの肝障害,癌の肝転移,肝臓における感染症,肝再生,肝移植片の拒絶・生着など,肝臓における免役反応において中心的な役割を果たす.
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| 4.
論文(リポジトリ) |
論文(リポジトリ)
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渡部, 久実 ; 飯合, 恒夫 ; 安保, 徹
概要:
Extrathymic T cells in mouse liver have TCR of intermediate intensity, contain doublenegative CD4^-CD8^- cells, and comprise forbidden self-reactive oligoclones. In the present study, we investigated how such extrathymic T cells
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were modulated during melanoma development in melanoma transgenic mice. Melanoma appeared in various organ of the transgenic mice at 15 wk of age. Extrathymic T cells with TCR of intermediate intensity increased in the liver, as the tumors advanced. Such cells infiltated the tumor lesions. In consequence of this study, it was proved that extrathymic T cells in the liver played important roles in tumor immunity.
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| 5.
論文(リポジトリ) |
論文(リポジトリ)
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大森, 克利
概要:
The thymus is the major central organ for T cell differentiation in the body. However attention was recently focused on an association of extrathymic T cells with various immune response. The liver is a major site for such extrathymic T
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cell differentiation. Cumulative evidences revealed that extrathymic T cells in the liver comprise cells with TCR of intermediate intensity and contain autoreactive clones. These extrathymic T cells were activated with aging and under conditions of bacterial stimulation and autoimmune diseases. In the present study, it was investigated how regular T cells were activated in mice injected with viable syngeneic tumors. It was demonstrated that specific activation of extrathymic T cells in the liver and acquisition of anti-tumor cytotoxicity were induced in these mice. The present results suggested that extrathymic T cells played an important role on tumor immunity in the host-defense mechanisms.
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| 6.
論文(リポジトリ) |
論文(リポジトリ)
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橋本, 誠雄
概要:
In a series of recent studies, extrathymic T cell differentiation in mice has been reported. These T cells may be more p
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rimitive than that of thymic origin. Since they carry self reactive forbidden clones, it could be benefical for elimenating their own atypical cells. They express IL-2Rβ similar to NK cells, containing CD4 or CD8 double negative cells. Their morphology is large granular lymphocyte (LGL). This study is to elucidate the possibility that CD56 positive T cells with a morphology of LGL are the counterpart of extrathymic T cells in human. CD56 positive T cells were abundant in the liver comparing in peripheral blood from same donor. The phenotype of T cells in the liver mononuclear cells (MNC), CD56 positive T cells had considerably higher proportion of TCR-γδ aquisition, and CD4, CD8 double negative population were also existed in one of the case who had high population of CD56 positive T cells. While CD56 positive cells were absent in the thymus. CD56 positive T cells were able to proliferate in serum-rich medium condition supplemented with IL-2. CD56 positive T cells were also harvested from bone marrow cells in a liquid culture without thymic environment. These results described above and similarities of the extrathymic T cells in mice, strongly indicate the possibility that CD56 positive T cells is a counterpart of extrathymic T cells in humans.
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| 7.
論文(リポジトリ) |
論文(リポジトリ)
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木村, 元彦
概要:
Male predominance of malignant disease and female predominance of autoimmune disease are widely known in humans. To eluc
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idate one of the underlying mechanisms, we examined whether sex differences exist at the level of extrathymic T cells in various organs of mice under physiological conditions. Effects of orchiectomy or testosterone administration were also examined. Extrathymic T cells expressing CD3 of intermediate intensity (i. e., intermediate TCR cells) and a high level of IL-2 receptor β-chain (IL-2Rβ), and thymusderived T cells expressing of TCR of bright intensity (i. e., bright TCR cells) and lacking IL-2Rβ, were identified by immunofluorescent tests. Of each three strain tested, it was demonstrated that intermediate TCR cells were much more predominant in the liver and some other organs in female mice than in male mice. In the liver of orchiectomied mice, the number of mononuclear cells increasod and intermediate TCR cells became predominant as if the mice were female. Testosterone replacement canceled the immunological effect of orchiectomy. Considering the fact that extrathymic T cells comprise a considerable proportion of self-reactive forbidden clones and possess cytotoxic activity aganinst syngenic tumor cells, the present results might suggest a possible relationship between physiologically low levels of extrathymic T cells and the male predominance of malignancy.
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| 8.
論文(リポジトリ) |
論文(リポジトリ)
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安保, 徹
概要:
免疫系は二層構造になっていることを明らかにしました. 生物が上陸した後に, 外来抗原向けにクローンを構成したのが, 新しい免疫系です. 胸腺や骨髄で作られるT細胞やB細胞です. 一方, 生物が上陸する以前から存在したのが古い免疫系です. 腸
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や肝臓で作られるNK細胞, 胸腺外分化T細胞, 自己抗体産生B-1細胞です. 私たちは, 若い時はT細胞, B細胞中心の免疫系で守られていますが, 加齢やストレスや細胞内寄生感染症が起こると, 古い免疫系に立ち戻ります. これによって異常自己を排除しているのです. 自己免疫疾患も免疫系の失敗や異常で起こっているのではありません. ストレス反応なのです. この時, 進化した新しい免疫系は抑制状態になっています. 治療の問題点にも気付けるでしょう.
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