Mohns Mariel S, Greene Justin M, Cain Brian T, Pham Ngoc H, Gostick Emma, Price David A, O'Connor David H
Department of Pathology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, United Kingdom.
J Virol. 2015 Oct;89(19):9748-57. doi: 10.1128/JVI.00993-15. Epub 2015 Jul 15.
CD8 T cells play a crucial role in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). However, the specific qualities and characteristics of an effective CD8 T cell response remain unclear. Although targeting breadth, cross-reactivity, polyfunctionality, avidity, and specificity are correlated with HIV control, further investigation is needed to determine the precise contributions of these various attributes to CD8 T cell efficacy. We developed protocols for isolating and expanding SIV-specific CD8 T cells from SIV-naive Mauritian cynomolgus macaques (MCM). These cells exhibited an effector memory phenotype, produced cytokines in response to cognate antigen, and suppressed viral replication in vitro. We further cultured cell lines specific for four SIV-derived epitopes, Nef103-111 RM9, Gag389-394 GW9, Env338-346 RF9, and Nef254-262 LT9. These cell lines were up to 94.4% pure, as determined by major histocompatibility complex (MHC) tetramer analysis. After autologous transfer into two MCM recipients, expanded CD8 T cells persisted in peripheral blood and lung tissue for at least 24 weeks and trafficked to multiple extralymphoid tissues. However, these cells did not impact the acute-phase SIV load after challenge compared to historic controls. The expansion and autologous transfer of SIV-specific T cells into naive animals provide a unique model for exploring cellular immunity and the control of SIV infection and facilitate a systematic evaluation of therapeutic adoptive transfer strategies for eradication of the latent reservoir.
CD8 T cells play a crucial role in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Autologous adoptive transfer studies followed by SIV challenge may help define the critical elements of an effective T cell response to HIV and SIV infection. We developed protocols for isolating and expanding SIV-specific CD8 T cells from SIV-naive Mauritian cynomolgus macaques. This is an important first step toward the development of autologous transfer strategies to explore cellular immunity and potential therapeutic applications in the SIV model.
CD8 T细胞在控制人类免疫缺陷病毒（HIV）和猴免疫缺陷病毒（SIV）方面发挥着关键作用。然而，有效的CD8 T细胞反应的具体特性和特征仍不清楚。尽管靶向广度、交叉反应性、多功能性、亲和力和特异性与HIV控制相关，但需要进一步研究以确定这些不同属性对CD8 T细胞功效的确切贡献。我们制定了从未感染SIV的毛里求斯食蟹猴（MCM）中分离和扩增SIV特异性CD8 T细胞的方案。这些细胞表现出效应记忆表型，对同源抗原产生细胞因子，并在体外抑制病毒复制。我们进一步培养了针对四个SIV衍生表位Nef103 - 111 RM9、Gag389 - 394 GW9、Env338 - 346 RF9和Nef254 - 262 LT9的细胞系。通过主要组织相容性复合体（MHC）四聚体分析确定，这些细胞系纯度高达94.4%。在自体转移到两名MCM受体后，扩增的CD8 T细胞在外周血和肺组织中持续存在至少24周，并迁移到多个淋巴外组织。然而，与历史对照相比，这些细胞在攻击后并未影响急性期SIV载量。将SIV特异性T细胞扩增并自体转移到未感染动物中，为探索细胞免疫和控制SIV感染提供了一个独特的模型，并有助于对根除潜伏库的治疗性过继转移策略进行系统评估。
CD8 T细胞在控制人类免疫缺陷病毒（HIV）和猴免疫缺陷病毒（SIV）方面发挥着关键作用。在SIV攻击后进行自体过继转移研究可能有助于确定对HIV和SIV感染的有效T细胞反应的关键要素。我们制定了从未感染SIV的毛里求斯食蟹猴中分离和扩增SIV特异性CD8 T细胞的方案。这是朝着开发自体转移策略以探索细胞免疫和在SIV模型中的潜在治疗应用迈出的重要第一步。
