Multifunctional human immunodeficiency virus (HIV) gag-specific CD8+ T-cell responses in rectal mucosa and peripheral blood mononuclear cells during chronic HIV type 1 infection
Multifunctional human immunodeficiency virus (HIV) gag-specific CD8+ T-cell responses in rectal mucosa and peripheral blood mononuclear cells during chronic HIV type 1 infection
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DOI：
10.1128/jvi.02535-06
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发表时间：
2007-06-01
影响因子：
5.4
通讯作者：
Shacklett, Barbara L.
中科院分区：
文献类型：
--
作者：
Critchfield, J. William;Lemongello, Donna;Shacklett, Barbara L.
肠道是一个富含淋巴细胞的部位，在猴免疫缺陷病毒或人类免疫缺陷病毒1型（HIV-1）感染后几天内，记忆性CD4(+) T细胞会严重耗竭。随后的病毒特异性CD8(+) T细胞的流入，在整个感染的慢性期持续存在，也被记录在胃肠道中。然而，对这些效应细胞的功能或它们与疾病进程的关系知之甚少。在这项研究中，我们测量了慢性感染患者配对直肠和血液样本中CD8(+) t细胞对HIV-1肽的反应。在血液和直肠中，与Pol和Env相比，CD8(+) t细胞对HIV Gag有免疫优势反应（P < 0.01）。相比之下，巨细胞病毒pp65肽在外周血单核细胞（PBMC）中强烈诱导γ干扰素（ifn - γ）分泌，而在直肠CD8(+) T细胞中较弱（P = 0.015）。在HIV肽的刺激下，来自两个位点的CD8(+) T细胞能够产生复杂的反应，包括脱颗粒（CD107表达）和ifn - γ和肿瘤坏死因子α (tnf - α)的产生。在直肠组织中，CD107的释放经常伴随着ifn - γ或tnf - α的产生。在未接受抗逆转录病毒治疗的患者中，直肠粘膜中gag特异性反应的大小（CD8(+) T细胞的百分比）大于PBMC (P = 0.054)；然而，在两个部位，反应细胞分解成特定的功能类别是相似的。这些发现表明，直肠CD8(+) T细胞能够产生强大而多样的hiv -1特异性反应，因此可能在慢性感染期间消除感染细胞中发挥积极作用。
The intestinal tract is a lymphocyte-rich site that undergoes severe depletion of memory CD4(+) T cells within days of simian immunodeficiency virus or human immunodeficiency virus type 1 (HIV-1) infection. An ensuing influx of virus-specific CD8(+) T cells, which persist throughout the chronic phase of infection, has also been documented in the gastrointestinal tract. However, little is known of the functionality of these effector cells or their relationship to the disease course. In this study, we measured CD8(+) T-cell responses to HIV-1 peptides in paired rectal and blood samples from chronically infected patients. In both blood and rectum, there was an immunodominant CD8(+) T-cell response to HIV Gag compared to Pol and Env (P < 0.01). In contrast, cytomegalovirus pp65 peptides elicited gamma interferon (IFN-gamma) secretion strongly in peripheral blood mononuclear cells (PBMC but weakly in rectal CD8(+) T cells (P = 0.015). Upon stimulation with HIV peptides, CD8(+) T cells from both sites were capable of mounting complex responses including degranulation (CD107 expression) and IFN-gamma and tumor necrosis factor alpha (TNF-alpha) production. In rectal tissue, CD107 release was frequently coupled with production of IFN-gamma or TNF-alpha. In patients not on antiretroviral therapy, the magnitude of Gag-specific responses, as a percentage of CD8(+) T cells, was greater in the rectal mucosa than in PBMC (P = 0.054); however, the breakdown of responding cells into specific functional categories was similar in both sites. These findings demonstrate that rectal CD8(+) T cells are capable of robust and varied HIV-1-specific responses and therefore likely play an active role in eliminating infected cells during chronic infection.