Hoq M M, Suzutani T, Toyoda T, Horiike G, Yoshida I, Azuma M
Department of Microbiology, Asahikawa Medical College, Japan.
J Gen Virol. 1997 Jul;78 ( Pt 7):1597-603. doi: 10.1099/0022-1317-78-7-1597.
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 immunosurveillance.
海藻糖6,6'-二甲苯磺酸盐（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。当给小鼠静脉注射TDM时，肉芽肿性肺中积累的少数带有γ/δ T细胞受体的T淋巴细胞（γδ T细胞）显著增殖，这被认为与维持对致死性流感病毒感染的获得性抵抗力有关。为了阐明抵抗流感病毒的细胞基础，在流感病毒感染前，通过体内注射相应抗体使小鼠的γδ T细胞、α/β（αβ）T细胞或自然杀伤（NK）细胞耗竭。γδ T细胞的耗竭显著消除了TDM处理小鼠增强的抗感染能力，αβ T细胞或NK细胞的耗竭也有同样的效果。为了深入了解γδ T细胞的功能能力，我们评估了该T细胞亚群对一组稳定转染了来自A/PR/8/34（H1N1）和A/爱知/2/68（H3N2）毒株的流感病毒血凝素（HA）基因的靶细胞系的细胞毒性活性。来自TDM处理小鼠的γδ T细胞以非主要组织相容性复合体限制的方式，对表达H1或H3亚型HA的靶细胞表现出显著的细胞毒性。综上所述，这些结果表明，γδ T细胞与αβ T细胞和NK细胞一起，在保护小鼠免受流感病毒感染方面发挥非特异性作用，并且活化的γδ T细胞对表达HA的靶细胞的识别和破坏是这种抗流感病毒免疫监视所涉及的步骤之一。
