Slifka M K, Pagarigan R R, Whitton J L
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
J Immunol. 2000 Feb 15;164(4):2009-15. doi: 10.4049/jimmunol.164.4.2009.
NK cells have been phenotypically defined by the expression of specific markers such as NK1.1, DX5, and asialo-GM1 (ASGM1). In addition to NK cells, a small population of CD3+ T cells has been shown to express these markers, and a unique subpopulation of NK1. 1+CD3+ T cells that expresses an invariant TCR has been named "NKT cells." Here, we describe NK marker expression on a broad spectrum of MHC class I- and MHC class II-restricted T cells that are induced after acute viral infection. From 5 to >500 days post lymphocytic choriomeningitis virus (LCMV) infection, more than 90% of virus-specific CD8+ and CD4+ T cells coexpress one or more of these three prototypical NK markers. Furthermore, in vivo depletion of NK cells with anti-ASGM1 Ab resulted in the removal of 90% of virus-specific CD8+ T cells and 50-80% of virus-specific CD4+ T cells. This indicates that studies using in vivo depletion to determine the role of NK cells in immune defense could potentially be misinterpreted because of the unintended depletion of Ag-specific T cells. These results demonstrate that NK Ags are widely expressed on the majority of virus-specific T cells and indicate that the NK and T cell lineages may not be as distinct as previously believed. Moreover, the current nomenclature defining NKT cells will require comprehensive modification to include Ag-specific CD8+ and CD4+ T cells that express prototypical NK Ags.
自然杀伤（NK）细胞已通过特定标志物的表达进行表型定义，如NK1.1、DX5和去唾液酸神经节苷脂1（ASGM1）。除NK细胞外，一小部分CD3⁺ T细胞也已被证明表达这些标志物，并且一种表达恒定T细胞受体的独特亚群NK1.1⁺CD3⁺ T细胞已被命名为“自然杀伤T（NKT）细胞”。在此，我们描述了急性病毒感染后诱导产生的广泛的主要组织相容性复合体（MHC）I类和MHC II类限制性T细胞上NK标志物的表达。在淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染后5天至超过500天，超过90%的病毒特异性CD8⁺和CD4⁺ T细胞共表达这三种典型NK标志物中的一种或多种。此外，用抗ASGM1抗体在体内清除NK细胞导致90%的病毒特异性CD8⁺ T细胞和50 - 80%的病毒特异性CD4⁺ T细胞被清除。这表明，由于意外清除了抗原特异性T细胞，使用体内清除法来确定NK细胞在免疫防御中的作用的研究可能会被误解。这些结果表明，NK抗原在大多数病毒特异性T细胞上广泛表达，并且表明NK细胞和T细胞谱系可能不像以前认为的那样截然不同。此外，当前定义NKT细胞的命名法需要全面修改，以纳入表达典型NK抗原的抗原特异性CD8⁺和CD4⁺ T细胞。
