ROLE OF NK CELLS IN SIV-INFECTED LONG-TERM NONPROGRESSING RHESUS MACAQUES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 中国恒河猴(CHRM)感染SIV可导致长期非进展性猕猴(LTNP)的高发。我们使用这个模型继续研究自然杀伤(NK)细胞在LTNP CHRM建立长期无进展状态中的作用。最近，为了研究SIV感染不同状态下NK细胞的基因表达情况，我们利用恒河猴特异性基因芯片进行了基因芯片检测。我们用CD8、CD16珠纯化了LTNP和正常进展者(NP)外周血中的NK细胞。CD16是一种低亲和力的受体，在晚期免疫反应中将免疫球蛋白识别为多价抗原周围的聚集体。值得注意的是，与NP相比，LTNP中的NK细胞上调了CD16(FcrRIIIa)的表达，CD16是ADCC免疫反应的重要基因。然而，下游的src家族激酶LCK/Fyn被下调，这可能会将整个NK细胞的激活调节到相对较低的水平。较低的NK细胞活性可能避免了诱导全身免疫激活，这可能是LTNP病毒状态较低的主要原因。NK细胞也表达大量的iNKR。尽管NK细胞途径的抑制既有上调(LILRB1、AIRM1、NKG2A)，也有下调(LAIR1)，但下游基因变化不大，表明在SIV感染的长期无进展状态下，NK细胞的抑制有微小的变化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. SIV infection in Chinese rhesus macaque (ChRM) results in high frequency of long-term nonprogressing macaques (LTNP). We used this model for continuous study of the role of natural killer (NK) cells in the establishment of long-term nonprogressing state in LTNP ChRM. Recently, to investigate gene expression in NK cells at different status of SIV infection, we used rhesus specific gene array chips for microarray assay. We purified NK cells in peripheral blood from the LTNP and normal progressors (NP) using CD8+, CD16+ beads. CD16 is a low affinity receptor that recognizes IgG as aggregates surrounding multivalent antigens during late immune responses. Remarkably, in comparison with NP, NK cells in LTNP had high up-regulation of CD16 (FcrRIIIa), the gene that was important for the ADCC immune responses. However, the downstream src-family kinase LCK/Fyn was downregulated that may moderate the overall NK cell activation to a relatively low level. Lower NK cell activation may avoid inducing general immune activation, which is possibly the main contributor of low viral status in the LTNP. NK cells also express numerous iNKR. Even though inhibition of NK cell pathway had both upregulation (LILRB1, AIRM1, NKG2A) and down-regulation (LAIR1), the downstream gene had minor changes, indicating minor changes of NK cell inhibition in the SIV-infected long-term nonprogressing status.