Vaccination with live attenuated simian immunodeficiency virus causes dynamic changes in intestinal CD4+CCR5+ T cells.

Vaccination with live attenuated simian immunodeficiency virus causes dynamic changes in intestinal CD4+CCR5+ T cells.
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DOI:
10.1186/1742-4690-8-8
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发表时间:
2011-02-03
期刊:
影响因子:
3.3
通讯作者:
Stebbings R
Stebbings R
中科院分区:
医学2区
文献类型:
--
作者:
Li B;Berry N;Ham C;Ferguson D;Smith D;Hall J;Page M;Quartey-Papafio R;Elsley W;Robinson M;Almond N;Stebbings R

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用减毒SIV活疫苗接种可以防止可检测到的野生型病毒感染。我们已经研究了靶细胞耗竭是否有助于观察到的保护。在用减毒活SIV接种后,在接种后第3、7、10、21和125天测定肠CD 4 + CCR 5 + T细胞(野生型SIV感染和破坏的早期靶标)的频率。在初始对照中,在LPL TTrM-1和IEL TTrM-2亚群中主要发现适度频率的肠CD 4 + CCR 5 + T细胞。在第3天,LPL和IEL CD 4 + CCR 5 + TEM细胞显著增加,而分化程度较低的亚群大大减少,与活化诱导的成熟一致。CCR 5表达在第7天仍然很高,尽管亚群平衡从CD 4 + CCR 5 + TEM转移到分化程度较低的TTrM-2细胞。肠道CD 4 + CCR 5 + T细胞的这种增加先于第10天测量的SIV RNA血浆负荷的峰值。在第10天,肠道CD 4 + CCR 5 + T细胞的消耗大于65.9%,但总体CD 4 + T细胞稳态由增加的CD 4 + CCR 5- T细胞维持。在第21天和第125天,检测到大量的肠道CD 4 + CCR 5-幼稚TN细胞,同时在第125天检测到大量增加的CD 4 + CCR 5 + LPL TTrM-2和IEL TEM细胞,但SIV RNA血浆载量仍然很低。减毒SIV活疫苗接种后,肠道CD 4 + CCR 5 + T细胞的增加与靶细胞耗竭(作为保护机制)无关。相反,肠道CD 4 + CCR 5 + T细胞的增加可能与减毒活SIV疫苗接种所提供的保护相关或起作用。
Vaccination with live attenuated SIV can protect against detectable infection with wild-type virus. We have investigated whether target cell depletion contributes to the protection observed. Following vaccination with live attenuated SIV the frequency of intestinal CD4+CCR5+ T cells, an early target of wild-type SIV infection and destruction, was determined at days 3, 7, 10, 21 and 125 post inoculation. In naive controls, modest frequencies of intestinal CD4+CCR5+ T cells were predominantly found within the LPL TTrM-1 and IEL TTrM-2 subsets. At day 3, LPL and IEL CD4+CCR5+ TEM cells were dramatically increased whilst less differentiated subsets were greatly reduced, consistent with activation-induced maturation. CCR5 expression remained high at day 7, although there was a shift in subset balance from CD4+CCR5+ TEM to less differentiated TTrM-2 cells. This increase in intestinal CD4+CCR5+ T cells preceded the peak of SIV RNA plasma loads measured at day 10. Greater than 65.9% depletion of intestinal CD4+CCR5+ T cells followed at day 10, but overall CD4+ T cell homeostasis was maintained by increased CD4+CCR5- T cells. At days 21 and 125, high numbers of intestinal CD4+CCR5- naive TN cells were detected concurrent with greatly increased CD4+CCR5+ LPL TTrM-2 and IEL TEM cells at day 125, yet SIV RNA plasma loads remained low. This increase in intestinal CD4+CCR5+ T cells, following vaccination with live attenuated SIV, does not correlate with target cell depletion as a mechanism of protection. Instead, increased intestinal CD4+CCR5+ T cells may correlate with or contribute to the protection conferred by vaccination with live attenuated SIV.
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