Radosevich Michael, Ono Santa Jeremy
Department of Immunology, University College London, University of London, Institute of Ophthalmology, London EC1V 9EL UK.
Immunol Res. 2004;30(2):125-38. doi: 10.1385/IR:30:2:125.
The major histocompatibility complex (MHC) class II transactivator (CIITA) typically is required for both constitutive and inducible expression of MHC class II genes. However, transcription of class II MHC genes has been observed in specific cell types (e.g., thymic epithelial cells) in CIITA-deficient mice as well as in specific situations (e.g., following viral infections or in natural killer [NK]/target cell interaction). These observations have been interpreted by some to indicate that a CIITA-independent pathway of class II gene expression might be germane to processes such as the acquisition of tolerance during thymic selection or in the evasion of immune surveillance by a subset of viruses. One of the most striking examples of CIITA-independent, inducible class II gene expression has involved the de novo expression of class II MHC molecules on respiratory epithelial cells following infection by human parainfluenza virus type 3 (HPIV3). We report here that despite careful analysis using multiple techniques, we have been unable to detect HPIV3-dependent, CIITA-independent (or CIITA-dependent) induction of class II MHC genes. Thus, whereas there may still be an intriguing role for CIITA-independent gene expression in facets of the immune response, this is unlikely to manifest in the analysis of HPIV3 infection of respiratory epithelial cells.
主要组织相容性复合体(MHC)II类反式激活因子(CIITA)通常是MHC II类基因组成型和诱导型表达所必需的。然而,在CIITA缺陷小鼠的特定细胞类型(如胸腺上皮细胞)以及特定情况下(如病毒感染后或自然杀伤[NK]/靶细胞相互作用时),已观察到II类MHC基因的转录。一些人将这些观察结果解释为,II类基因表达的CIITA非依赖途径可能与胸腺选择过程中的耐受获得或某些病毒逃避免疫监视等过程相关。CIITA非依赖的、可诱导的II类基因表达最显著的例子之一,涉及人3型副流感病毒(HPIV3)感染后呼吸道上皮细胞上II类MHC分子的从头表达。我们在此报告,尽管使用多种技术进行了仔细分析,但我们仍无法检测到HPIV3依赖的、CIITA非依赖(或CIITA依赖)的II类MHC基因诱导。因此,虽然CIITA非依赖基因表达在免疫反应的某些方面可能仍有有趣的作用,但这在呼吸道上皮细胞的HPIV3感染分析中不太可能体现出来。