IMMUNE RESTORATION AND PROTECTION IN SIV-INFECTED LONG TERM NONPROGRESSORS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 SIVmac感染中国恒河猴导致高频率的长期非进展者（LTNP）。我们比较了细胞因子/趋化因子谱，SIV特异性细胞和体液免疫反应之间的SIV感染的中国恒河猴，无论是LTNP或正常进展。到目前为止，我们已经使用Bio-Cells细胞因子试剂盒检测了2个进展者和1个LTNP的纵向血浆样品中的细胞因子水平。一个进展者在感染后第28天具有显著降低的TNF-α和IL-15，并且在感染后第90天具有增加的TNF-α、IL-6和IL-12。该动物在设定点时具有最高的血浆病毒载量，并在1.5年内发展为AIDS。LTNP具有非常稳定的细胞因子水平，除了在感染后第28天TNF-α和IL-15的轻微降低。有趣的是，LTNP始终显示出比进展者显著更高水平的趋化因子嗜酸性粒细胞趋化因子（CCL 11），一种CCR 3配体。通过微阵列分析，在另一LTNP中也观察到eotaxin mRNA的上调。在LTNP中，CCAAT/增强子结合蛋白δ（C/EBP δ）在CD 8 + T细胞中也显著上调。所有SIV感染的动物引起可变水平的SIV特异性抗体应答Env和Gag的ELISA。细胞内细胞因子染色显示LTNP中SIVgag特异性CD 4和CD 8 + T细胞应答比进展者更强。除了SIV特异性CD 4和CD 8 + T细胞和抗体应答外，CCL 11和C/EBP δ在维持SIV感染长期不进展中的作用值得进一步研究。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. SIVmac infection in Chinese rhesus macaques leads to a high frequency of long-term nonprogressors (LTNP). We compared the cytokine/chemokine profiles, and SIV specific cellular and humoral immune responses between SIV infected Chinese rhesus that are either LTNP or normal progressor. Thus far we have examined levels of cytokines in longitudinal plasma samples of 2 progressors and one LTNP using Bio-Plex Cytokine kit. One progressor had significantly decreased TNF-alpha and IL-15 at day 28, and increased TNF-alpha, IL-6 and IL-12 at day 90 post infection. This animal had the highest plasma viral load at set point and developed AIDS in 1.5 years. The LTNP had very stable levels of cytokines except a minor reduction of TNF-alpha and IL-15 at day 28 p.i. Interestingly, the LTNP consistently displayed significantly higher levels of the chemokine eotaxin (CCL11), a CCR3 ligand, than the progressor. The upregulation of eotaxin mRNA was also observed in another LTNP by microarray assay. The CCAAT/enhancer binding protein delta (C/EBP delta) was also significantly upregulated in CD8+ T cells in the LTNP. All SIV-infected animals elicited variable levels of SIV specific antibody responses to Env and Gag by ELISA. Intracellular cytokine staining showed stronger SIVgag-specific CD4 and CD8+ T cell responses in LTNP than progressors. In addition to SIV-specific CD4 and CD8+ T cells and antibody responses, the role of CCL11 and C/EBP delta merit further investigation in the maintenance of long-term nonprogression in SIV infection.