Minimally invasive monitoring of CD4 T cells at multiple mucosal tissues after intranasal vaccination in rhesus macaques.
Minimally invasive monitoring of CD4 T cells at multiple mucosal tissues after intranasal vaccination in rhesus macaques.
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DOI：
10.1371/journal.pone.0188807
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Sastry KJ
中科院分区：
文献类型：
--
作者：
Dorta-Estremera S;Nehete PN;Yang G;He H;Nehete BP;Shelton KA;Barry MA;Sastry KJ
在非人灵长类动物（NHP）中进行的感染和/或疫苗接种后前瞻性免疫细胞监测研究通常依赖于定期采集血液样本，由于安全性问题和实际限制，仅偶尔采集粘膜组织活检。在这里，我们提出的证据支持口腔，直肠和生殖器粘膜组织的细胞刷采样作为一种微创的方法，不同的T细胞亚群从头表型分析，以及前瞻性鼻内免疫后，恒河猴。显著百分比的活淋巴细胞一致地从幼稚和慢性SIV感染的恒河猴获得。血液中的CD 3 + T细胞百分比显著高于未处理动物中分析的粘膜组织中的百分比，而在SIV+动物中，相对于分析的所有其他部位，直肠组织中的CD 3 + T细胞显著升高。在未感染过SIV的猕猴中，与口腔粘膜和血液相比，直肠和阴道粘膜组织中表达HIV进入共受体CCR 5和粘膜特异性粘附（CD 103）以及活化（HLA-DR）和增殖（Ki 67）标记物的CD 4 + T细胞的多样性和百分比更高。在一项正在进行的研究中，对SIV+动物进行口腔、直肠和生殖器粘膜组织的连续每日细胞刷采样，其中对这些动物鼻内接种含有绿色荧光蛋白（GFP）报告基因的腺病毒载体疫苗。我们检测到一个短暂的增加，GFP+ CD 4 T细胞仅在口腔粘膜表明有限的粘膜运输。一般而言，表达Ki 67的CD 4+和CD 8 + T细胞在所有粘膜组织中瞬时增加，但表达CCR 5、HLA-DR和CD 103标记物的T细胞表现出微小变化。我们提出了微创细胞刷采样作为一种实用的方法，有效和前瞻性的免疫监测的口腔生殖器粘膜组织在NHP。
Studies in nonhuman primates (NHP) for prospective immune cell monitoring subsequent to infection and/or vaccination usually rely on periodic sampling of the blood samples with only occasional collections of biopsies from mucosal tissues because of safety concerns and practical constraints. Here we present evidence in support of cytobrush sampling of oral, rectal, and genital mucosal tissues as a minimally invasive approach for the phenotypic analyses of different T cells subsets de novo as well as prospectively after intranasal immunization in rhesus macaques. Significant percentages of viable lymphocytes were obtained consistently from both naïve and chronically SIV-infected rhesus macaques. The percentages of CD3+ T cells in the blood were significantly higher compared to those in the mucosal tissues analyzed in the naïve animals, while in the SIV+ animals the CD3+ T cells were significantly elevated in the rectal tissues, relative to all other sites analyzed. In the naïve, but not SIV+ macaques, the rectal and vaginal mucosal tissues, compared to oral mucosa and blood, showed higher diversity and percentages of CD4+ T cells expressing the HIV entry co-receptor CCR5 and mucosal specific adhesion (CD103) as well as activation (HLA-DR) and proliferation (Ki67) markers. Sequential daily cytobrush sampling from the oral, rectal, and genital mucosal tissues was performed in SIV+ animals from an ongoing study where they were administered intranasal immunization with adenoviral vectored vaccines incorporating the green fluorescent protein (GFP) reporter gene. We detected a transient increase in GFP+ CD4 T cells in only oral mucosa suggesting limited mucosal trafficking. In general, CD4+ and CD8+ T cells expressing Ki67 transiently increased in all mucosal tissues, but those expressing the CCR5, HLA-DR, and CD103 markers exhibited minor changes. We propose the minimally invasive cytobrush sampling as a practical approach for effective and prospective immune monitoring of the oral-genital mucosal tissues in NHP.
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影响因子：
3.7
作者：
Weaver EA;Nehete PN;Nehete BP;Yang G;Buchl SJ;Hanley PW;Palmer D;Montefiori DC;Ferrari G;Ng P;Sastry KJ;Barry MA
通讯作者：
Barry MA
DOI：
10.1007/978-1-4939-1115-8_24
发表时间：
2014-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Singh, Shailbala;Nehete, Pramod;Sastry, K Jagannadha
通讯作者：
Sastry, K Jagannadha
影响因子：
4.4
作者：
McKinnon, Lyle R.;Nyanga, Billy;Kaul, Rupert
通讯作者：
Kaul, Rupert
影响因子：
168.9
作者：
Buchbinder, Susan P.;Mehrotra, Devon V.;Duerr, Ann;Fitzgerald, Daniel W.;Mogg, Robin;Li, David;Gilbert, Peter B.;Lama, Javier R.;Marmor, Michael;del Rio, Carlos;McElrath, M. Juliana;Casimiro, Danilo R.;Gottesdiener, Keith M.;Chodakewitz, Jeffrey A.;Corey, Lawrence;Robertson, Michael N.
通讯作者：
Robertson, Michael N.
影响因子：
5.4
作者：
Tenbusch, Matthias;Ignatius, Ralf;Uberla, Klaus
通讯作者：
Uberla, Klaus