Factors determining T lineage commitment in haematopoietic stem cell.

决定造血干细胞T谱系定型的因素。

• 批准号: 16390045
• 负责人: ITOH Tsunetoshi
• 金额: $ 9.54万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390045/
• 关键词: Thymus; Hematopoietic stem cells; Lineage commitment; Microenvironment; Cytokine; T lymphocyte

T lymphocytes differentiate and mature in the thymus. It has been still controversial whether multi-potent haematopoietic stem cells (HSCs) enter the thymus or progenitors committed to T cell lineage do. It remains also unknown how HSCs are committed to T cell lineage, how a small number of T cells are selected or how mature T cell receptor (TCR) repertoire is formed. Using electron micrographic and immunohistochemical studies, we attempted to isolate HSCs in the thymus of CTS mice (sister strain to NOD, defect in emigration of mature T cells from the thymus to periphery). By using molecular biological technique, we studied thymocyte development and thymic selection in different strains of mice. Novel findings were revealed through these studies.1. We took more than ten thousand electron micrographs and frequently found neutrophils and eosinophils at the stage of development from the myelocyte to the metamyelocyte in the thymic parenchyma. We also isolated erythroids (reticulocytes, er … More ythrocytes) and megakaryocytes. This is the first report to demonstrate that presence of megakaryocytes in thymus, suggesting multi-lineage HSCs enter into the thymus. Cytokine production supporting hematopoiesis in the thymus was confirmed with RT-PCR. Collectively, these results suggest that multi-lineage HSCs immigrate into the thymus.2. TCR repertoire is largely different among different strains of mice in mature thymocytes but not in immature thymocytes at earlier stages. This suggests that pre-selection TCR repertoire is determined by some genetic factors conserved among mouse strains.3. We demonstrated that CDR3 length shortening was occurred in both CD4SP and CD8SP. The extent of CDR3 shortening was remarkable in CD4SP than in CD8SP and varied among different strains of mice, suggesting that the CDR3 shortening was influenced by MHC haplotype. The CDR3 shortening was dependent on V segment. We assumed that structural feature of Vbeta segment encoded in germline impacts on CDR3 length. Less

T淋巴细胞在胸腺内分化成熟。多能造血干细胞(HSCs)是否进入胸腺，或致力于T细胞谱系的祖细胞是否进入胸腺仍存在争议。目前尚不清楚造血干细胞是如何致力于T细胞谱系的，少数T细胞是如何被选择的，或者成熟的T细胞受体(TCR)是如何形成的。用电子显微镜和免疫组织化学方法分离CTS小鼠胸腺中的HSCs(NOD的姊妹株，成熟T细胞从胸腺向外周游走缺陷)。利用分子生物学技术，对不同品系小鼠胸腺细胞发育和胸腺选择进行了研究。通过这些研究发现了新的发现1。我们拍摄了一万多张电子显微镜照片，在胸腺实质中经常发现中性粒细胞和嗜酸性粒细胞处于从髓细胞到偏粒细胞的发育阶段。我们还分离了红系(网织红细胞，呃…更多的人)和巨核细胞。这是首次报道胸腺中存在巨核细胞，提示多系HSC进入胸腺。RT-PCR证实胸腺产生支持造血的细胞因子。总体而言，这些结果表明，多系造血干细胞迁移到胸腺。不同品系的小鼠在成熟胸腺细胞中的TCR谱有很大差异，但在早期的未成熟胸腺细胞中没有明显差异。这表明预选TCR谱带是由小鼠品系间保守的一些遗传因素决定的。我们发现CD4SP和CD8SP都存在CDR3长度缩短。CD4SP的CDR3缩短程度显著高于CD8SP，且在不同品系小鼠之间存在差异，提示CDR3缩短受MHC单倍型的影响。CDR3缩短依赖于V段。我们推测胚系编码的Vbeta片段的结构特征对CDR3长度有影响。较少

项目成果

Alteration of T cell receptor repertoires during thymic development

胸腺发育过程中 T 细胞受体库的改变

• 发表时间: 2006
• 期刊: Scandinavian Journal of Immunology (印刷中)
• 作者: Abe J;Hosokawa H;Sawada Y;Matsumura K;Kobayashi S;Shino Nakamura-Kikuoka;Takaji Matsutani
• 通讯作者: Takaji Matsutani

Alterations of T cell receptor repertoire and CDR3 length

T 细胞受体库和 CDR3 长度的改变

• 发表时间: 2006
• 期刊: Japanese Journal of Lymphology (in press)
• 作者: Abe J;Hosokawa H;Sawada Y;Matsumura K;Kobayashi S;Shino Nakamura-Kikuoka;Takaji Matsutani;松谷 隆治;Shino Nakamura-Kikioka;Takaji Matsutani;Takaji Matsutani
• 通讯作者: Takaji Matsutani

胸腺選択によるT細胞受容体レパトアとCDR3長の変化

胸腺选择导致 T 细胞受体库和 CDR3 长度的变化

• 发表时间: 2006
• 期刊: リンパ学 (印刷中)
• 作者: Abe J;Hosokawa H;Sawada Y;Matsumura K;Kobayashi S;Shino Nakamura-Kikuoka;Takaji Matsutani;松谷 隆治
• 通讯作者: 松谷 隆治

WBN/Kob-Ht rats spontaneously develop dermatitis under conventional conditions:: Another possible model for atopic dermatitis

• DOI: 10.1538/expanim.54.461
• 发表时间: 2005-10-01
• 期刊: EXPERIMENTAL ANIMALS
• 影响因子: 2.4
• 作者: Asakawa, M;Yoshioka, T;Horikawa, T
• 通讯作者: Horikawa, T

Accumulation of intestinal intraepithelial lymphocytes in association with lack of polymeric immunoglobulin receptor

肠道上皮内淋巴细胞的积累与缺乏聚合免疫球蛋白受体有关

• 发表时间: 2005
• 期刊: European Journal of Immunology 35・4
• 作者: Abe J;Hosokawa H;Sawada Y;Matsumura K;Kobayashi S;Shino Nakamura-Kikuoka;Takaji Matsutani;松谷 隆治;Shino Nakamura-Kikioka;Takaji Matsutani;Takaji Matsutani;Shino Nakamura-Kikuoka S;松谷 隆治;Makoto Asakawa;Ken-ichi Yamazaki
• 通讯作者: Ken-ichi Yamazaki