Induction of a virus-specific effector-memory CD4+ T cell response by attenuated SIV infection.
Induction of a virus-specific effector-memory CD4+ T cell response by attenuated SIV infection.
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DOI：
10.1084/jem.20060134
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发表时间：
2006-11-27
期刊：
影响因子：
--
通讯作者：
Johnson RP
中科院分区：
文献类型：
--
作者：
Gauduin MC;Yu Y;Barabasz A;Carville A;Piatak M;Lifson JD;Desrosiers RC;Johnson RP
我们研究了猴免疫缺陷病毒（SIV）特异性CD4+ T细胞反应在恒河猴慢性感染减毒或致病性SIV毒株。对SIVΔnef-infected动物的分析显示，SIV特异性CD4+ T细胞的频率相对较高，占所有针对多种SIV蛋白的CD4+ T淋巴细胞的4-10%。野生型siv感染动物中gag特异性CD4+ T细胞的出现频率低5 - 10倍，且与血浆病毒血症水平呈负相关。来自SIVΔnef动物的siv特异性CD4+细胞主要是CD27 - CD28 - CD45RAlowCCR7 - CCR5 -，与效应记忆亚群一致，并包括完全分化的CD45RA+CCR7 -亚群。相比之下，来自siv感染动物的siv特异性CD4+ T细胞主要是CD27+CD28+CD45RA - CCR7+CCR5+，与早期中枢记忆表型一致。通过SIV Gag刺激后溶酶体膜蛋白CD107a的穿孔素表达和上调，SIVΔnef动物的CD45RA+CCR7−CD4+亚群对效应CD4+ T细胞高度富集。减毒siv感染动物的siv特异性CD4+ T细胞在细支气管肺泡灌洗中出现频率增加，在淋巴结中出现频率减少，这与效应记忆T细胞群一致。SIVΔnef诱导具有直接效应功能的高频病毒特异性CD4+ T细胞应答的能力可能在接种减毒SIV毒株产生的保护性免疫中发挥关键作用。
We investigated simian immunodeficiency virus (SIV)-specific CD4+ T cell responses in rhesus macaques chronically infected with attenuated or pathogenic SIV strains. Analysis of SIVΔnef-infected animals revealed a relatively high frequency of SIV-specific CD4+ T cells representing 4–10% of all CD4+ T lymphocytes directed against multiple SIV proteins. Gag-specific CD4+ T cells in wild-type SIV-infected animals were 5–10-fold lower in frequency and inversely correlated with the level of plasma viremia. SIV-specific CD4+ cells from SIVΔnef animals were predominantly CD27−CD28−CD45RAlowCCR7−CCR5−, consistent with an effector–memory subset, and included a fully differentiated CD45RA+CCR7− subpopulation. In contrast, SIV-specific CD4+ T cells from SIV-infected animals were mostly CD27+CD28+CD45RA−CCR7+CCR5+, consistent with an early central memory phenotype. The CD45RA+CCR7−CD4+ subset from SIVΔnef animals was highly enriched for effector CD4+ T cells, as indicated by the perforin expression and up-regulation of the lysosomal membrane protein CD107a after SIV Gag stimulation. SIV-specific CD4+ T cells in attenuated SIV-infected animals were increased in frequency in bronchioalveolar lavage and decreased in lymph nodes, consistent with an effector–memory T cell population. The ability of SIVΔnef to induce a high frequency virus-specific CD4+ T cell response with direct effector function may play a key role in protective immunity produced by vaccination with attenuated SIV strains.
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影响因子：
5.4
作者：
Iwashiro, M;Peterson, K;Hasenkrug, KJ
通讯作者：
Hasenkrug, KJ
影响因子：
5.4
作者：
Johnson, RP;Glickman, RL;Desrosiers, RC
通讯作者：
Desrosiers, RC
影响因子：
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作者：
Boaz, MJ;Waters, A;Vyakarnam, A
通讯作者：
Vyakarnam, A
影响因子：
5.4
作者：
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通讯作者：
Desrosiers, RC
影响因子：
5.4
作者：
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通讯作者：
Marx, PA