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。次级项目的主要支助 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 为子项目列出的总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 SIV感染中国恒河猴（ChRM）导致高频率的长期非进展性猕猴（LTNP）。我们用这个模型连续研究自然杀伤（NK）细胞在LTNP ChRM建立长期非进展状态中的作用。最近，为了研究SIV感染不同状态下NK细胞的基因表达，我们使用恒河猴特异性基因芯片进行微阵列检测。我们使用CD8+、CD16+珠从LTNP和正常进展者（NP）的外周血中纯化NK细胞。CD16是一种低亲和力受体，其在晚期免疫应答期间将IgG识别为围绕多价抗原的聚集体。值得注意的是，与NP相比，LTNP中的NK细胞具有CD16（FcrRIIIa）的高度上调，该基因对于ADCC免疫应答是重要的。然而，下游src家族激酶LCK/Fyn下调，这可能将整体NK细胞活化调节至相对较低的水平。较低的NK细胞活化可以避免诱导全身免疫活化，这可能是LTNP中低病毒状态的主要贡献者。NK细胞还表达许多iNKR。尽管NK细胞通路的抑制有上调（LILRB 1、AIRM1、NKG2A）和下调（LAIR 1），但下游基因有微小的变化，表明在SIV感染的长期非进展状态下NK细胞抑制的微小变化。

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.