Institut National de la Santé et de la Recherche Médicale (INSERM), U768, 75015 Paris, France.
Immunol Rev. 2010 May;235(1):10-23. doi: 10.1111/j.0105-2896.2010.00890.x.
The granule-dependent cytotoxic activity of lymphocytes plays a critical role in the defense against virally infected cells and tumor cells. The importance of this cytotoxic pathway in immune regulation is evidenced by the severe and often fatal condition, known as hemophagocytic lymphohistiocytic syndrome (HLH) that occurs in mice and humans with genetically determined impaired lymphocyte cytotoxic function. HLH manifests as the occurrence of uncontrolled activation of T lymphocytes and macrophages infiltrating multiple organs. In this review, we focus on recent advances in the characterization of effectors regulating the release of cytotoxic granules, and on the role of this cytotoxic pathway in lymphocyte homeostasis and immune surveillance. Analysis of the mechanisms leading to the occurrence of hemophagocytic syndrome designates gamma-interferon as an attractive therapeutic target to downregulate uncontrolled macrophage activation, which sustains clinical and biological features of HLH.
淋巴细胞的颗粒依赖性细胞毒性活性在抵御病毒感染细胞和肿瘤细胞方面起着至关重要的作用。这种细胞毒性途径在免疫调节中的重要性，从遗传决定的淋巴细胞细胞毒性功能受损的小鼠和人类中发生的严重且常致命的疾病，即噬血细胞性淋巴组织细胞增生症 (HLH) 中得到了证明。HLH 表现为 T 淋巴细胞和浸润多个器官的巨噬细胞的失控激活。在这篇综述中，我们重点介绍了近年来在鉴定调节细胞毒性颗粒释放的效应子方面的进展，以及该细胞毒性途径在淋巴细胞稳态和免疫监视中的作用。对导致噬血细胞综合征发生的机制的分析将γ干扰素指定为一种有吸引力的治疗靶点，以下调失控的巨噬细胞激活，从而维持 HLH 的临床和生物学特征。
