Hayward A, Laszlo M, Vafai A
Department of Pediatrics, University of Colorado School of Medicine, Denver 80262.
J Immunol. 1989 Feb 15;142(4):1139-43.
Deficient responses by NK cells may contribute to the susceptibility of human newborns to severe HSV infections. Furthermore, HSV disseminates widely during neonatal infection and may also infect and interfere with the function of blood mononuclear cells (MNC). To determine whether the function of newborn NK cells would be affected by contact with HSV, and whether newborn NK cells might be permissive for HSV replication, newborn MNC were cultured with HSV in vitro for 3 days. Before culture, the intracellular calcium mobilization in newborn NK cells induced by mAb to CD2 and CD16 did not differ from that of adult NK cells. This result argues against immaturity of an early NK cell activation event in human newborns. After culture with HSV the Ca2+ flux response was unaffected by lysis of K562 targets by newborn NK cells and NK-dependent suppression of HSV replication in fibroblasts were preserved or increased. Incorporation of thymidine by NKH-1 cells following stimulation with PHA and IL-2 was not suppressed. NK cells recovered from these cultures did not contain infectious HSV and synthesis of HSV-specific proteins was not detected by immunoprecipitation although HSV genome was detected by DNA hybridization. Our results extend the in vitro model stimulation systems in which newborn NK cells respond positively to include triggering through the CD2 Ag, cross-linking of cell surface CD 16 Ag and response to a pathogen, HSV.
自然杀伤细胞(NK细胞)反应不足可能导致人类新生儿易患严重的单纯疱疹病毒(HSV)感染。此外,HSV在新生儿感染期间广泛传播,还可能感染并干扰血液单核细胞(MNC)的功能。为了确定新生儿NK细胞的功能是否会受到与HSV接触的影响,以及新生儿NK细胞是否可能允许HSV复制,将新生儿MNC与HSV在体外培养3天。培养前,用抗CD2和CD16单克隆抗体诱导的新生儿NK细胞内钙动员与成人NK细胞无异。这一结果反驳了人类新生儿早期NK细胞激活事件不成熟的观点。与HSV共培养后,Ca2+通量反应不受新生儿NK细胞对K562靶细胞的杀伤作用影响,且NK细胞对成纤维细胞中HSV复制的依赖性抑制作用得以保留或增强。PHA和IL-2刺激后NKH-1细胞的胸腺嘧啶核苷掺入未受抑制。从这些培养物中回收的NK细胞不含感染性HSV,尽管通过DNA杂交检测到HSV基因组,但免疫沉淀未检测到HSV特异性蛋白的合成。我们的结果扩展了体外模型刺激系统,其中新生儿NK细胞对包括通过CD2抗原触发、细胞表面CD16抗原交联以及对病原体HSV的反应在内的刺激呈阳性反应。