Gastrointestinal T lymphocytes retain high potential for cytokine responses but have severe CD4+ T-cell depletion at all stages of simian immunodeficiency virus infection compared to peripheral lymphocytes
Gastrointestinal T lymphocytes retain high potential for cytokine responses but have severe CD4+ T-cell depletion at all stages of simian immunodeficiency virus infection compared to peripheral lymphocytes
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DOI：
10.1128/jvi.72.8.6646-6656.1998
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发表时间：
1998-08-01
影响因子：
5.4
通讯作者：
Dandekar, S
中科院分区：
文献类型：
--
作者：
Smit-McBride, Z;Mattapallil, JJ;Dandekar, S
人类免疫缺陷病毒（HIV）感染的胃肠道并发症是肠粘膜免疫系统受损的标志。我们使用猴免疫缺陷病毒（SIV）感染的恒河猴作为HIV的动物模型，以确定SIV对肠道T淋巴细胞的致病作用。在SIV感染期间检测肠道CD 4（+）T细胞耗竭和细胞因子应答的可能性，并与淋巴结和血液中淋巴细胞的结果进行比较。流式细胞术分析表明，在SIV感染的整个过程中，肠道固有层淋巴细胞（LPL）和上皮内淋巴细胞（IEL）中的CD 4（+）CD 8（-）单阳性T细胞和CD 4（+）CD 8（+）双阳性T细胞严重减少。相反，外周淋巴结和血液中的CD 4 + T细胞消耗是逐渐的。细胞内γ干扰素（IFN-γ）和白细胞介素-4（IL-4）的生产后，短期促有丝分裂激活的流式细胞仪分析显示，LPL保留相同或更高的能力，IFN-γ生产在所有阶段的SN感染相比，未感染的控制，而外周血单核细胞显示逐渐下降。CD 8（+）T细胞是IFN-γ的主要产生者。LPL和外周血单个核细胞中IL-4产生细胞的频率没有可检测的变化。因此，在原发性SN感染中，CD 4（+）LPL和IEL的严重耗竭伴随细胞因子应答的改变，可能反映了肠粘膜中T细胞稳态的改变，这可能是SIV相关肠病和病毒发病机制的一种机制。肠道T淋巴细胞的动态变化在外周淋巴结或血液中没有得到充分的代表。
Gastrointestinal complications in human immunodeficiency virus (HIV) infection are indicative of impaired intestinal mucosal immune system. We used simian immunodeficiency virus (SIV)-infected rhesus macaques as an animal model for HIV to determine pathogenic effects of SIV on intestinal T lymphocytes. Intestinal CD4(+) T-cell depletion and the potential for cytokine responses were examined during SIV infection and compared with results for lymphocytes from lymph nodes and blood. Flow cytometric analysis demonstrated severe depletion of CD4(+)CD8(-) single-positive T cells and CD4(+)CD8(+) double-positive T cells in intestinal lamina propria lymphocytes (LPL) and intraepithelial lymphocytes (IEL) during primary SIV infection which persisted through the entire course of SIV infection. In contrast, CD4+ T-cell depletion was gradual in peripheral lymph nodes and blood. Flow cytometric analysis of intracellular gamma interferon (IFN-gamma) and interleukin-4 (IL-4) production following short-term mitogenic activation revealed that LPL retained same or higher capacity for IFN-gamma production in all stages of SN infection compared to uninfected controls, whereas peripheral blood mononuclear cells displayed a gradual decline. The CD8(+) T cells were the major producers of IFN-gamma. There was no detectable change in the frequency of IL-4-producing cells in both LPL and peripheral blood mononuclear cells. Thus, severe depletion of CD4(+) LPL and IEL in primary SN infection accompanied by altered cytokine responses may reflect altered T-cell homeostasis in intestinal mucosa, This could be a mechanism of SIV-associated enteropathy and viral pathogenesis. Dynamic changes in intestinal T lymphocytes were not adequately represented in peripheral lymph nodes or blood.