Durable Mucosal Simian Immunodeficiency Virus-Specific Effector Memory T Lymphocyte Responses Elicited by Recombinant Adenovirus Vectors in Rhesus Monkeys
Durable Mucosal Simian Immunodeficiency Virus-Specific Effector Memory T Lymphocyte Responses Elicited by Recombinant Adenovirus Vectors in Rhesus Monkeys
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DOI：
10.1128/jvi.05346-11
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发表时间：
2011-11-01
影响因子：
5.4
通讯作者：
Barouch, Dan H.
中科院分区：
文献类型：
--
作者：
Li, Hualin;Liu, Jinyan;Barouch, Dan H.
在外周和粘膜组织中诱导有效和持久的细胞免疫应答对于开发针对人类免疫缺陷病毒1型和其他病原体的有效疫苗可能是重要的。特别是，在粘膜表面的效应器响应可能是至关重要的快速响应传入的粘膜病原体。在这里，我们报告称，将非复制型重组腺病毒（rAd）载体肌肉注射到恒河猴体内，可诱导显着持久的猿猴免疫缺陷病毒（SIV）特异性T淋巴细胞反应，该反应在外周血和多种粘膜组织（包括结直肠、十二指肠）中持续2年以上。阴道活检标本，以及支气管肺泡灌洗液。在外周血中，SIV特异性T淋巴细胞经历了预期的表型演变，从效应记忆T细胞（T（EM））到中央记忆T细胞（TCM）接种后。相反，粘膜SIV特异性T淋巴细胞表现出持久和持久的T（EM）表型，不随时间推移而演变。这些数据表明，非复制型rAd载体诱导持久的和广泛分布的效应记忆粘膜T淋巴细胞反应的表型不同于外周T淋巴细胞反应。疫苗引起的T（EM）在粘膜表面的反应可能被证明是至关重要的，提供保护，防止入侵的病原体在粘膜入口。
The induction of potent and durable cellular immune responses in both peripheral and mucosal tissues may be important for the development of effective vaccines against human immunodeficiency virus type 1 and other pathogens. In particular, effector responses at mucosal surfaces may be critical to respond rapidly to incoming mucosal pathogens. Here we report that intramuscular injection of nonreplicating recombinant adenovirus (rAd) vectors into rhesus monkeys induced remarkably durable simian immunodeficiency virus (SIV)-specific T lymphocyte responses that persisted for over 2 years in both peripheral blood and multiple mucosal tissues, including colorectal, duodenal, and vaginal biopsy specimens, as well as bronchoalveolar lavage fluid. In peripheral blood, SIV-specific T lymphocytes underwent the expected phenotypic evolution from effector memory T cells (T(EM)) to central memory T cells (TCM) following vaccination. In contrast, mucosal SIV-specific T lymphocytes exhibited a persistent and durable T(EM) phenotype that did not evolve over time. These data demonstrate that nonreplicating rAd vectors induce durable and widely distributed effector memory mucosal T lymphocyte responses that are phenotypically distinct from peripheral T lymphocyte responses. Vaccine-elicited T(EM) responses at mucosal surfaces may prove critical for affording protection against invading pathogens at the mucosal portals of entry.