Cellular mechanisms of graft rejection mediated by CD4-CD8-TCR alphabeta T cells.

CD4-CD8-TCR Alphata T 细胞介导的移植物排斥的细胞机制。

• 批准号: 04454210
• 负责人: NAKAYAMA Eiichi
• 金额: $ 0.77万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454210/
• 关键词: CTL; CD4^-CD8^-TCR alphabeta CTL; CD8-depletion; MHC class I antigen; MHC class I-restricted antigen; 腫瘍拒絶抗原; MHC拘束性; CD4^-CD8^-TCRαβ; 移植免疫; T細胞; CD4^-CD8^-; TCRのβ

Generation of in vitro CD4^-CD8^-TCR alphabeta CTL response against allogeneic MHC class I antigen and MHC class I-restricted antigen was investigated. We demonstrated that in mice that were depleted of CD8^+ cells, CD4^-CD8^-TCR alphabeta CTL were induced against allogeneic MHC class I antigen following activation of CD4^+ cells. On the other hand, against MHC-class I restricted antigen, CD8-depleted mice were incapable of generating CTL response. However, when target cells were MHC class II (and I) antigen positive cells, CTL with both CD4^+ and CD4^-CD8^-TCR alphabeta phenotypes were generated in CD8-depleted B6 mice. Thus, in this case, stimulation of CD4^+ T cells by MHC class II restricted antigen leads to generation of CD4^-CD8^-TCR alphabeta CTL specific for MHC class I restricted antigen. Moreover, CD4^-CD8^-TCR alphabeta CTL are capable of mediating rejection responses in vivo.

观察CD4^-CD8^-TCR α - CTL对同种异体MHC I类抗原和MHC I类限制性抗原的体外反应。我们证明了在CD8^+细胞缺失的小鼠中，CD4^-CD8^-TCR α - CTL在CD4^+细胞激活后被诱导对抗同种异体MHC I类抗原。另一方面，针对mhc - I类限制性抗原，cd8缺失小鼠不能产生CTL反应。然而，当靶细胞是MHC II类（和I类）抗原阳性细胞时，cd8缺失的B6小鼠产生CD4^+和CD4^-CD8^-TCR α β表型的CTL。因此，在这种情况下，MHC II类限制性抗原刺激CD4^+ T细胞导致产生CD4^-CD8^-TCR α CTL特异性MHC I类限制性抗原。此外，CD4^-CD8^-TCR α - CTL在体内能够介导排斥反应。

项目成果

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Morita, A., et al.：“TL 抗原作为移植抗原，被 TL 限制性细胞毒性 T 细胞识别。”

Uenaka, A., et al.: "Roles of CD8^+ and CD4^+ cells on lethal graft-versus-host disease in nude mice." Transplant Immunol.1,2. 132-136 (1993)

Uenaka, A. 等人：“CD8+ 和 CD4+ 细胞在裸鼠致死性移植物抗宿主病中的作用。”

中山 睿一: "免疫実験操作法" 南江堂(分担執筆) (印刷中),

Ruiichi Nakayama：《免疫学实验操作方法》Nankodo（撰稿人）（出版中），

Mineno, M., et al.: "CD4^-CD8^-T cell receptor alphabeta T cells : Generation of an in vitro major histocomptibility complex class I specific dytotoxic T lymphocyte response and allogenic tumor rejection." J.Exp. Med.174. 193-201 (1991)

Mineno, M., 等人：“CD4^-CD8^-T 细胞受体 Alphata T 细胞：体外主要组织相容性复合物 I 类特异性细胞毒性 T 淋巴细胞反应和同种异体肿瘤排斥的产生。”

Yamaguchi, J., et al.: "Long teerm survival of orthotopic LEW liver grafts in WF rats : elimination or inactivation of effector CTL and alteredantigenicity as possible reasons for tolerance." Transplantation. 57. 412-418 (1994)

Yamaguchi, J. 等人：“WF 大鼠原位 LEW 肝移植物的长期存活：效应 CTL 的消除或失活以及抗原性的改变可能是耐受性的原因。”