Role of gamma delta TCR+ lymphocytes in the augmented resistance of trehalose 6,6'-dimycolate-treated mice to influenza virus infection
Role of gamma delta TCR+ lymphocytes in the augmented resistance of trehalose 6,6'-dimycolate-treated mice to influenza virus infection
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DOI：
10.1099/0022-1317-78-7-1597
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发表时间：
1997-07-01
影响因子：
3.8
通讯作者：
Azuma, M
中科院分区：
文献类型：
--
作者：
Hoq, MM;Suzutani, T;Azuma, M
海藻糖6，6 '-二霉菌酸酯（TDM）是一种免疫调节剂，可增强小鼠对流感病毒感染的非特异性抵抗力。当小鼠静脉注射TDM时，少数携带γ/δ T细胞受体（γ δ T细胞）的T淋巴细胞在肉芽肿性肺中积累的显著增殖被认为与维持对致命流感病毒感染的获得性抗性有关。为了阐明针对流感病毒的防御的细胞基础，通过在流感病毒感染之前体内施用相应的抗体来耗尽小鼠的γ δ T细胞、α/β（α β）T细胞或自然杀伤（NK）细胞。γ δ T细胞的耗竭显著消除了TDM处理的小鼠对感染的增强的抵抗力，α β T细胞或NK细胞的耗竭也是如此。为了深入了解γ δ T细胞的功能能力，我们评估了该T细胞亚群对一组靶细胞系的细胞毒性活性，所述靶细胞系用来自A/PR/8/34（H1N1）和A/Aichi/2/68（H3 N2）毒株的流感病毒血凝素（HA）基因稳定转染。来自TDM处理的小鼠的γ δ T细胞以非主要组织相容性复合物限制的方式显示出对表达H1或H3亚型HA的靶细胞的显著细胞毒性。总之，这些结果表明，γ δ T细胞与α β T细胞和NK细胞一起在保护小鼠免受流感病毒感染中发挥非特异性作用，并且活化的γ δ T细胞对HA表达靶细胞的识别和破坏是参与这种抗流感病毒免疫监视的步骤之一。
Trehalose 6,6'-dimycolate (TDM), an immunomodulator, potentiates non-specific resistance in mice to influenza virus infection. When mice were injected intravenously with TDM, the striking proliferation of a minority of T-lymphocytes bearing gamma/delta T-cell receptors (gamma delta T-cells) that accumulated in granulomatous lungs was thought to be associated with the maintenance of acquired resistance to lethal influenza virus infection. To clarify the cellular basis of the defence against influenza virus, mice were depleted of gamma delta T-cells, alpha/beta (alpha beta) T-cells, or natural killer (NK) cells by in vivo administration of corresponding antibodies prior to influenza virus infection. The depletion of gamma delta T-cells significantly abrogated the augmented resistance of TDM-treated mice to infection, as did depletion of either alpha beta T-cells or NK cells. To gain insight into the functional ability of gamma delta T-cells, we evaluated the cytotoxic activity of this T-cell subset against a panel of target cell lines that were stably transfected with the influenza virus haemagglutinin (HA) gene from A/PR/8/34(H1N1) and A/Aichi/2/68(H3N2) strains. The gamma delta T-cells from TDM-treated mice showed profound cytotoxicity against the target cells expressing HA of either the H1 or H3 subtype, in a non-major histocompatibility complex-restricted manner. Taken together, these results indicate that gamma delta T-cells play a non-specific role, in conjunction with alpha beta T-cells and NK cells, in protecting mice against influenza virus infection, and that the recognition and destruction of HA-expressing target cells by the activated gamma delta T-cells is one of the steps involved in this anti-influenza virus immuno-surveillance.