The roles of gammadelta T cells in host defense aginst bacterial infection
The roles of gammadelta T cells in host defense aginst bacterial infection
批准号:
02454191
负责人:
YOSHIKAI Yasunobu
金额:
$4.29万
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
项目状态:
已结题
起止时间:
1990 至 1992
中文摘要
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。
英文摘要
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.
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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。
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通讯作者:
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)
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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)
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Inoue,T.,et al.: "Early appearing γδ-bearing T cells during infectin with Calmette Guerin Bacillus." J.Immunol.146. 2754-2762 (1991)
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Tauchi,Y.,et al.: "A new subpopulation of intestinal intraepithelial lymphocytes expressing high level of TcRγδ recognize IE^<k.>" Eur.J.Immunol.22. 2465-2468 (1992)
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共 84 条
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财政年份:1998
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依托单位:
海外基金