CD20 DEPLETION IN SIVSMM-INFECTED RHESUS MACAQUES

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来源获得了主要资金， 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。 我们的小组鉴定并表征了一种对自体和异源血清中和高度敏感的SIVsmm株（SIVsmmD 215）。我们使用该中和株研究了抗体中和对SIV复制的影响。 用100 TCID 50的SIVsmD 215接种13只Rh。7只动物在第10天用50 mg/kg的rituxan（一种抗CD 20抗体）治疗， SIVsmmD 215感染后7、14、35和56。另6只作为对照，仅接受SIVsmmD 215。检测外周血、淋巴结和肠道中病毒复制（VL）和主要淋巴细胞亚群的动态。血清学检查比较两组抗SIV抗体的差异。 研究组中的所有动物均成功去除外周血中的CD 20细胞。三只动物仅部分耗尽LN和肠中的CD 20细胞。CD 20缺失的Rh猴和对照猴之间的VL没有显著差异：峰值VL范围为10^6至3 x 10^8 SIV RNA拷贝/ml。在感染的慢性期，两组显示出相似的病毒复制控制（设定点VL为10^2至10^4 SIV RNA拷贝/ml）。在CD 20耗尽的Rh组中存在较低设定点VL的趋势。SIVsmm血清转化在肠和LN中CD 20完全耗尽的动物中延迟。细胞免疫应答在晚期时间点相似;与对照组相比，CD 20耗竭Rh感染早期CD 20耗竭猕猴的细胞免疫应答较高，可能是峰后阶段VL控制的原因。 总之，我们已经表明，CD 20耗竭在慢性感染阶段SIV病毒复制的控制中没有显着的作用。尽管在所有动物中，外周中的消耗是完全的，但是通过在病毒复制的主要位点处的CD 20消耗的功效预测抗体产生的缺乏

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. Our group identified and characterized an SIVsmm strain (SIVsmmD215) that is highly susceptible to neutralization by autologous and heterologous sera. We investigated the impact of antibody neutralization on SIV replication using this neutralizing strain. Thirteen Rh were inoculated with 100 TCID50 of SIVsmD215. Seven were treated with 50 mg/kg with rituxan (an anti-CD20 antibody) at days 7, 14, 35 and 56 post-SIVsmmD215 infection. The other 6 were used as a controls and received SIVsmmD215 only. The dynamics of viral replication (VL) and major lymphocyte subsets were measured in peripheral blood, lymph nodes (LNs) and intestine. Serology was performed to compare the differences in emergence of anti-SIV antibodies between the two groups. All the animals in the study group were successfully depleted of CD20 cells in peripheral blood. Three animals only partially depleted CD20 cells in the LNs and the intestine. There was no significant difference in VLs between CD20 depleted Rh and control monkeys: peak VLs ranged from 10^6 to 3 x 10^8 SIV RNA copies/ml. During the chronic phase of infection, both groups showed similar control of viral replication (set-point VLs of 10^2 to 10^4 SIV RNA copies/ml). There was a tendency for lower set-point VLs in the group of CD20-depleted Rh. SIVsmm seroconversion was delayed in the animals for which the CD20 depletion was complete in the intestine and LNs. Cellular immune responses were similar at late time-points; higher in CD20-depleted macaques early in infection between CD20-depleted Rh comparing to the control group and may have accounted for the control of VL during the post-peak stage. In conclusion, we have shown that CD20 depletion plays no significant role in the control of SIV viral replication during the chronic stage of infection. Although depletion is complete in the periphery in all the animals, the lack of antibody production is predicted by the efficacy of CD20 depletion at the main site of viral replication