Vaccine Induction of Lymph Node-Resident Simian Immunodeficiency Virus Env-Specific T Follicular Helper Cells in Rhesus Macaques.
Vaccine Induction of Lymph Node-Resident Simian Immunodeficiency Virus Env-Specific T Follicular Helper Cells in Rhesus Macaques.
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DOI：
10.4049/jimmunol.1502137
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发表时间：
2016-02-15
期刊：
影响因子：
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通讯作者：
Robert-Guroff M
中科院分区：
文献类型：
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作者：
Vargas-Inchaustegui DA;Demers A;Shaw JM;Kang G;Ball D;Tuero I;Musich T;Mohanram V;Demberg T;Karpova TS;Li Q;Robert-Guroff M
恒河猴抗原特异性T滤泡辅助细胞（TFH）活性的测量以前没有报道。考虑到恒河猴是评价HIV/SIV候选疫苗保护效力的首选动物模型，并且TFH细胞在帮助B细胞成熟中起关键作用，定量HIV/SIV特异性TFH细胞的疫苗诱导将极大地有益于疫苗开发。在此，我们在非人灵长类动物疫苗研究中首次定量了SIV Env特异性产生IL-21的TFH细胞。用编码SIV Env、Rev、Gag和Nef的腺病毒5宿主范围突变体（Ad 5 hr）重组体粘膜引发猕猴两次，随后用单体SIV gp 120或寡聚体SIV gp 140蛋白进行两次肌内加强。在第二次蛋白质加强后两周，我们获得淋巴结活组织检查并定量总的和SIV Env特异性IL-21+ TFH细胞和总的生发中心（GC）B细胞的频率、GC的大小和数量以及B细胞区中SIV特异性抗体分泌细胞的频率。多重相关性分析确定了TFH对全身和粘膜局部区室（包括血液、骨髓和直肠）中B细胞应答的重要性。我们的研究结果表明，SIV特异性TFH细胞，最初由复制Ad重组引发诱导，是长寿的。SIV Env特异性TFH细胞与全身和粘膜SIV特异性B细胞应答的多重相关性表明，在HIV疫苗开发中应进一步研究该细胞群体作为免疫的新相关性。
Measurement of antigen-specific T follicular helper (TFH) cell activity in rhesus macaques has not previously been reported. Given that rhesus macaques are the animal model of choice for evaluating protective efficacy of HIV/SIV vaccine candidates and that TFH cells play a pivotal role in aiding B cell maturation, quantifying vaccine-induction of HIV/SIV-specific TFH cells would greatly benefit vaccine-development. Here we quantified SIV Env-specific IL-21-producing TFH cells for the first time in a non-human primate vaccine study. Macaques were primed twice mucosally with Adenovirus 5 host range mutant (Ad5hr) recombinants encoding SIV Env, Rev, Gag and Nef followed by two intramuscular boosts with monomeric SIV gp120 or oligomeric SIV gp140 proteins. Two weeks after the second protein boost we obtained lymph node biopsies and quantified the frequency of total and SIV Env-specific IL-21+ TFH cells and total germinal center (GC) B cells, the size and number of GCs, and the frequency of SIV-specific antibody secreting cells in B cell zones. Multiple correlation analyses established the importance of TFH for development of B cell responses in systemic and mucosally localized compartments including blood, bone marrow, and rectum. Our results suggest that the SIV-specific TFH cells, initially induced by replicating Ad-recombinant priming, are long-lived. The multiple correlations of SIV Env-specific TFH cells with systemic and mucosal SIV-specific B cell responses indicate that this cell population should be further investigated in HIV vaccine development as a novel correlate of immunity.