Allogeneic Lymphocytes Persist and Traffic in Feral MHC-Matched Mauritian Cynomolgus Macaques
Allogeneic Lymphocytes Persist and Traffic in Feral MHC-Matched Mauritian Cynomolgus Macaques
复制标题
DOI：
10.1371/journal.pone.0002384
复制
发表时间：
2008-06-11
期刊：
影响因子：
3.7
通讯作者：
O'Connor, David H.
中科院分区：
文献类型：
--
作者：
Greene, Justin M.;Burwitz, Benjamin J.;O'Connor, David H.
背景资料：到目前为止，减毒SIV活疫苗是最成功的方法接种猕猴对致病性SIV的挑战，但是，目前还不清楚是什么机制负责这种保护。在小鼠中的连续转移研究对于理解活减毒疫苗在如Friend病毒的模型中的保护作用是不可或缺的。以前的过继转移灵长类动物已经失败，因为转移的细胞通常在transfer.Methodology/Principal Findings后几个小时内清除：在这里，我们描述了过继转移研究中的猕猴（MCM），非人灵长类动物模型有限的MHC多样性。在无关的MHC匹配的猕猴之间转移的细胞持续至少14天，但在MHC不匹配的猕猴中在36小时内被排斥。细胞从血液中贩运到外周淋巴组织transfer.Conclusions/Significance的12小时内：MHC匹配的MCM提供了第一个可行的灵长类动物模型过继转移研究。由于感染SIV的猕猴是研究HIV/AIDS发病机制的最佳模型，我们现在可以直接研究对AIDS病毒的保护性免疫反应的相关性。例如，在先前用减毒SIV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。淋巴细胞亚群从接种疫苗的供体连续转移到SIV未感染的动物中可能会定义负责保护的免疫机制，并指导未来的疫苗开发。
Background: 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-naive animals may define the immune mechanisms responsible for protection and guide future vaccine development.