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首页> 外文期刊>AIDS >Adenovirus vector-specific T cells demonstrate a unique memory phenotype with high proliferative potential and coexpression of CCR5 and integrin alpha4beta7.
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Adenovirus vector-specific T cells demonstrate a unique memory phenotype with high proliferative potential and coexpression of CCR5 and integrin alpha4beta7.

机译：腺病毒载体特异性T细胞表现出独特的记忆表型，具有高增殖潜能，并共同表达CCR5和整联蛋白alpha4beta7。

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BACKGROUND: The Step Study was a randomized trial to reduce HIV infection through vaccination with an adenovirus type 5 (Ad5)-based gag/polef construct; analysis following early cessation of the trial revealed an excess of HIV seroconversion in Ad5 seropositive men. This led to the suggestion that the Ad based vector may boost the number of CD4 chemokine receptor 5 (CCR5) T cells, target cells for HIV infection. OBJECTIVES: We sought to determine the immunophenotype and proliferative capacity of Ad5-specific T cells in the peripheral blood of adult donors to determine whether stimulation with replication defective Ad5 vectors could result in the significant expansion of a CD4 CCR5 T-cell subset. METHODS: Ad5-specific T cells were identified in the peripheral blood of healthy donors by interferon-gamma secretion assay and proliferative response was measured by carboxyfluorescein succinimidyl ester labelling. Cells were analyzed by flow cytometry to determine T-cell differentiation marker, CCR5 and alpha4beta7 expression on memory and proliferated cells. RESULTS: Ad5-specific CD4 T cells within healthy adult donors exhibit a unique minimally differentiated memory phenotype with coexpression of CD45RA, CD45RO and CCR7. Stimulation with Ad vector leads to rapid expansion in vitro and a switch to an effector memory phenotype. Both short-term reactivated and proliferating Ad5-specific CD4 T cells express the HIV coreceptor CCR5 and the HIV gp120-binding integrin alpha4beta7. CONCLUSION: Ad5-specific T cells demonstrate a phenotype and proliferative potential that would support HIV infection; these results are pertinent to the findings of the Step Study and future use of Ad5 as a vaccine vector.
机译：背景：本步骤研究是一项随机试验，旨在通过接种基于5型腺病毒（Ad5）的gag / pol / nef结构疫苗来减少HIV感染;在试验的早期停止后进行的分析显示，Ad5血清反应阳性男性的HIV血清转化过多。这提示了基于Ad的载体可能会增加CD4趋化因子受体5（CCR5）T细胞（HIV感染的靶细胞）的数量。目的：我们试图确定成年供体外周血中Ad5特异性T细胞的免疫表型和增殖能力，以确定用复制缺陷型Ad5载体刺激是否会导致CD4 CCR5 T细胞亚群的显着扩增。方法：通过干扰素-γ分泌法在健康供体外周血中鉴定出Ad5特异性T细胞，并通过羧基荧光素琥珀酰亚胺酯标记法检测增殖反应。通过流式细胞术分析细胞，以测定记忆和增殖细胞上的T细胞分化标志物，CCR5和α4beta7表达。结果：健康成人供体中的Ad5特异性CD4 T细胞表现出独特的最低分化记忆表型，并与CD45RA，CD45RO和CCR7共表达。用Ad载体刺激可导致体外快速扩增，并转换为效应子记忆表型。短期重新激活和增殖的Ad5特异性CD4 T细胞都表达HIV共受体CCR5和HIV gp120结合整联蛋白alpha4beta7。结论：Ad5特异性T细胞表现出支持HIV感染的表型和增殖潜能。这些结果与逐步研究的结果以及Ad5作为疫苗载体的未来用途有关。

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