The roles of gammadelta T cells in host defense aginst bacterial infection

γδ T 细胞在宿主防御细菌感染中的作用

• 批准号: 02454191
• 负责人: YOSHIKAI Yasunobu
• 金额: $ 4.29万
• 依托单位: Nagoya University (1991-1992)Kyushu University (1990)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454191/
• 关键词: Salmonella; Listeria; Mycobacteria; gammadeltaTcells; 65kdHSP; Cytokine; Host defense; 感染防御; ビルレンス; Ity遺伝子; HSP60; γδT細胞; 大腸菌

T cells recognize nominal antigens in the context of self-MHC antigens by T cell receptor(TcR) which is composed of alpha and beta chains. Another type of TcR, which is composed of gamma and delta chains has also identified. At least a significant fraction of gamma/delta T cells are reported to be specialized to recognize epitopes on mycobacterial antigens, suggesting that the gamma/delta bearing T cells may participate in immune surveillance against invasion with the various pathogens.To elucidate a potential role of the gamma/delta T cells in host-defense against bacterial infection,we examined the kinetics of gamma/delta T cells and their ligands during intraperitoneal infections with Listeria monocytogenes, Salmonella chorelaesuis and BCG.During infection with such intracellular bacteria, TcR gamma/delta T cells specific for 65kd hsp precede TcR alpha/beta T cells specific for bacterial antigens in appearance. The gamma/delta T cells provide a first line of defense against the infection by recognizing exogenous and endogenous 65 kd hsp on infected cells and producing cytokines such as gammaIFN. Our results suggest that the hsp- specific gamma/delta T cells respond quickly to antigenically diverse pathogens before antigen-specific alpha/beta T cells expand clonally, and they play a role in covering the gap between the phagocytic system and highly evolved immune response mediated by alpha/beta T cells.

T细胞通过由α链和β链组成的T细胞受体(TCR)在自身MHC抗原的背景下识别标称抗原。另一种类型的TCR也被发现，它由伽马链和增量链组成。据报道，至少有相当一部分的伽马/德尔塔T细胞专门识别分枝杆菌抗原的表位，这表明携带伽马/德尔塔的T细胞可能参与了对各种病原体入侵的免疫监视。为了阐明伽马/德尔塔T细胞在宿主防御细菌感染中的潜在作用，我们研究了单增李斯特菌、沙门氏菌和BCG腹腔感染过程中伽玛/德尔塔T细胞及其配体的动力学。在感染这些细胞内细菌的过程中，针对65kd热休克蛋白的TCR伽马/德尔塔T细胞先于针对细菌抗原的TCRα/βT细胞出现。γ/Delta T细胞通过识别感染细胞上的外源性和内源性65kd热休克蛋白，并产生细胞因子，如伽马干扰素，提供了抵御感染的第一道防线。我们的结果表明，在抗原特异性的α/βT细胞克隆扩增之前，HSP特异性的伽马/德尔塔T细胞对抗原性不同的病原体迅速做出反应，它们在覆盖吞噬系统和由α/βT细胞介导的高度进化的免疫反应之间起到了一定的作用。

项目成果

Kobayashi,N.,Matsuzaki,G.,Yoshikai,Y.,Seki,R.,Ivanyi,J.,and Nomoto,K.: "V region repertoire and ligands of antoreactive gammadelta^+ T cells" J.Immunol. (1993)

Kobayashi,N.、Matsuzaki,G.、Yoshikai,Y.、Seki,R.、Ivanyi,J. 和 Nomoto,K.：“抗反应性 γδT 细胞的 V 区库和配体”J.Immunol。

Yoshikai,Y.,et al.: "Bone marrow-derived cells are essential for intrathymic deletion of self-reactive T cells in both the host and donor-derived thymocytes of fully allogeneic bone marrow chimeras." J.Immunol.145. 505-509 (1990)

Yoshikai, Y. 等人：“在完全同种异体骨髓嵌合体的宿主和供体来源的胸腺细胞中，骨髓来源的细胞对于胸腺内自我反应性 T 细胞的删除至关重要。”

Iwasaki,A.,et al.: "Self-reactive T cell are Activated by the 65-kDa mycobacterial heat-shock protein in neonatally thymectomized mice." Eur.J.Immunol.21. 597-603 (1991)

Iwasaki,A.,et al.：“在新生胸腺切除小鼠中，自身反应性 T 细胞被 65 kDa 分枝杆菌热休克蛋白激活。”

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Tauchi，Y.，等人：“表达高水平 TcRγδ 的肠上皮内淋巴细胞的新亚群识别 IE^<k.>”Eur.J.Immunol.22（1992）。