Abnormality of signal Transduction via T-cell receptors mediated by retrovirus infection

逆转录病毒感染介导的T细胞受体信号转导异常

• 批准号: 02670283
• 负责人: YASUKAWA Masaki
• 金额: $ 1.34万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670283/
• 关键词: Immunodeficiency; Retrovirus; T-cell receptor; Cytotoxicity; signal transduction; HTLVーI; 細胞障害性; 細胞内カルシウムイオン

In order to clarify the mechanism of immunodeficiency mediated by human retrovirus infection, we investigated the functional alterations of T cells following infection with human T lymphotropic virus type I (HTLV-I), which is the causative agent of adult T-cell leukemia. Herpes simplex virus-specific CD4+ and CD8+ human cytotoxic T-cell (CTL) clones and T-cell receptor-gammadelta + T-cell clones were established. These clones were infected with HTLV-I by co-culture with a HTLV-I-producing T cell line. During the continuous culture of HTLV-I-infected T-cell clones, two distinct phases were observed in terms of cytotoxic activity and expression of the CD3-TCR complex. Early after HTLV-I infection, CTL lost their cytotoxic activity, but this was restored by the addition of lectin. At this time, no differences were observed in the expression of various surface molecules between HTLV-I-infected and uninfected parent cells, except for increased expression of CD25 on HTLV-I-infected cells. On the other hand, late after HTLV-I infection, the cytotoxicity, of HTLV-I-infected cells was almost completely lost, even in the presence of lectin, and expression of the CD3-TCR complex on the cell surface was markedly decreased. Concomitant with the decreased expression of CD3-TCR complex, a decrease in the elevation of cytoplasmic Ca2+ concentration induced by anti-CD3 and anti-TCR monoclonal antibodies was also observed. Our present findings thus show that T-cell functions are profoundly affected by HTLV-I infection through at least two distinct phases.

为了阐明人类逆转录病毒感染介导的免疫缺陷的机制，我们研究了用人T淋巴机病毒（HTLV-I）感染T细胞的功能改变，这是成人T细胞白血病的病因。建立了单纯疱疹病毒特异性CD4+和CD8+人类细胞毒性T细胞（CTL）克隆和T细胞受体-Gammadelta+ T细胞克隆。这些克隆通过与HTLV-I-I-I-I-I-I-I-I-I-I-I-I的T细胞系一起感染HTLV-I。在HTLV-I感染的T细胞克隆的连续培养过程中，在CD3-TCR复合物的细胞毒性活性和表达方面观察到了两个不同的阶段。 HTLV-1感染后的早期，CTL失去了细胞毒性活性，但通过添加凝集素来恢复。目前，除了在HTLV-I感染细胞上CD25的表达增加外，HTLV-I感染和未感染的母细胞之间各种表面分子的表达尚无差异。另一方面，HTLV-1感染后的后期，即使在存在凝集素的情况下，HTLV-I感染细胞的细胞毒性几乎完全丢失，并且CD3-TCR复合物在细胞表面的表达显着降低。随着CD3-TCR复合物的表达降低，还观察到抗CD3诱导的细胞质Ca2+浓度升高和抗TCR单克隆抗体的升高。因此，我们目前的发现表明，T细胞功能通过至少两个不同的阶段受到HTLV-I感染的深刻影响。

项目成果

Akira Inatsuki: "The effect of human T cell leukaemia virus type I infection on a herpes simplex virus-specific CD8+ cytotoxic T cell clone" British Journal of Haematology. 77. 311-314 (1991)

Akira Inatsuki：“人类 T 细胞白血病病毒 I 型感染对单纯疱疹病毒特异性 CD8 细胞毒性 T 细胞克隆的影响”英国血液学杂志。

Masaki Yasukawa, Akira Inatsuki, Takahiko Horiuchi, and Yuzuru Kobayashi: "Functional heterogeneity among herpes simplex virus-specific human CD4+ T cells." Journal of Immunology. 146. 1341-1347 (1991)

Masaki Yasukawa、Akira Inatsuki、Takahiko Horiuchi 和 Yuzuru Kobayashi：“单纯疱疹病毒特异性人类 CD4 T 细胞之间的功能异质性。”

Masaki Yasukawa, Akira Inatsuki, Yoshihiro Yakushijin, and Yuzuru Kobayashi: "Human T-cell leukemia virus type I (HTLV-I) infection of T cells bearing T-cell receptor gammadelta : effects of HTLV-I infection on cytotoxicity." International Journal of Canc

Masaki Yasukawa、Akira Inatsuki、Yoshihiro Yakushijin 和 Yuzuru Kobayashi：“携带 T 细胞受体 γδ 的 T 细胞的人类 T 细胞白血病病毒 I 型 (HTLV-I) 感染：HTLV-I 感染对细胞毒性的影响。”

Masaki Yasukawa: "Human T-cell leukemia virus type I (HTLV-I) infection of T cells bearing T-cell receptor-:effects of HTLV-I infection on cytotoxicity" International Journal of Cancer. 50. 431-437 (1992)

Masaki Yasukawa：“携带 T 细胞受体的 T 细胞的人类 T 细胞白血病病毒 I 型 (HTLV-I) 感染：HTLV-I 感染对细胞毒性的影响”国际癌症杂志。

Masaki Yasukawa,et al.: "Functional heterogeneity among herpes simplex virusーspecific human CD4+ T cell Clones" Journal of Immunology. (1991)

Masaki Yasukawa 等人：“单纯疱疹病毒特异性人 CD4+ T 细胞克隆之间的功能异质性”免疫学杂志（1991）。