Greene Justin M, Burwitz Benjamin J, Blasky Alex J, Mattila Teresa L, Hong Jung Joo, Rakasz Eva G, Wiseman Roger W, Hasenkrug Kim J, Skinner Pamela J, O'Connor Shelby L, O'Connor David H
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
PLoS One. 2008 Jun 11;3(6):e2384. doi: 10.1371/journal.pone.0002384.
Thus far, live attenuated SIV has been the most successful method for vaccinating macaques against pathogenic SIV challenge; however, it is not clear what mechanisms are responsible for this protection. Adoptive transfer studies in mice have been integral to understanding live attenuated vaccine protection in models like Friend virus. Previous adoptive transfers in primates have failed as transferred cells are typically cleared within hours after transfer.
METHODOLOGY/ PRINCIPAL FINDINGS: Here we describe adoptive transfer studies in Mauritian origin cynomolgus macaques (MCM), a non-human primate model with limited MHC diversity. Cells transferred between unrelated MHC-matched macaques persist for at least fourteen days but are rejected within 36 hours in MHC-mismatched macaques. Cells trafficked from the blood to peripheral lymphoid tissues within 12 hours of transfer.
CONCLUSIONS/SIGNIFICANCE: MHC-matched MCM provide the first viable primate model for adoptive transfer studies. Because macaques infected with SIV are the best model for HIV/AIDS pathogenesis, we can now directly study the correlates of protective immune responses to AIDS viruses. For example, plasma viral loads following pathogenic SIV challenge are reduced by several orders of magnitude in macaques previously immunized with attenuated SIV. Adoptive transfer of lymphocyte subpopulations from vaccinated donors into SIV-naïve animals may define the immune mechanisms responsible for protection and guide future vaccine development.
迄今为止，减毒活SIV一直是给猕猴接种疫苗以抵御致病性SIV攻击的最成功方法；然而，尚不清楚是什么机制导致了这种保护作用。在小鼠中进行的过继转移研究对于理解像Friend病毒这样的模型中的减毒活疫苗保护作用至关重要。先前在灵长类动物中进行的过继转移均告失败，因为转移的细胞通常在转移后数小时内就被清除。
方法/主要发现：在此，我们描述了在毛里求斯起源的食蟹猴（MCM）中进行的过继转移研究，MCM是一种MHC多样性有限的非人类灵长类动物模型。在不相关的MHC匹配的猕猴之间转移的细胞至少持续十四天，但在MHC不匹配的猕猴中在36小时内被排斥。转移后12小时内，细胞从血液运输到外周淋巴组织。
结论/意义：MHC匹配的MCM为过继转移研究提供了首个可行的灵长类动物模型。由于感染SIV的猕猴是艾滋病毒/艾滋病发病机制的最佳模型，我们现在可以直接研究针对艾滋病病毒的保护性免疫反应的相关因素。例如，在用减毒SIV预先免疫的猕猴中，致病性SIV攻击后的血浆病毒载量降低了几个数量级。将来自接种疫苗供体的淋巴细胞亚群过继转移到未感染SIV的动物中，可能会确定负责保护的免疫机制，并指导未来的疫苗开发。
