Irreversible depletion of intestinal CD4+ T cells is associated with T cell activation during chronic HIV infection.
Irreversible depletion of intestinal CD4+ T cells is associated with T cell activation during chronic HIV infection.
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DOI：
10.1172/jci.insight.146162
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发表时间：
2021-11-22
期刊：
影响因子：
8
通讯作者：
Kløverpris HN
中科院分区：
文献类型：
--
作者：
Asowata OE;Singh A;Ngoepe A;Herbert N;Fardoos R;Reddy K;Zungu Y;Nene F;Mthabela N;Ramjit D;Karim F;Govender K;Ndung'u T;Porterfield JZ;Adamson JH;Madela FG;Manzini VT;Anderson F;Leslie A;Kløverpris HN
人类胃肠道（GI）中的HIV感染被认为是HIV进展的核心，但这种相互作用的知识主要限于西方国家的队列。在这里，我们提出了一个大的队列招募从高艾滋病毒流行地区在南非和发现，艾滋病毒感染者（PLWH）提出在一个年轻的年龄在GI诊所的调查。我们发现胃肠道中存在严重的CD 4 + T细胞耗竭，小肠中的耗竭程度高于大肠，且与抗逆转录病毒治疗（ART）或血浆病毒血症的年限无关。HIV-p24染色显示持续的病毒表达，特别是在结肠中，尽管血浆病毒血症完全抑制。粘膜抗逆转录病毒（ARV）药物的定量显示，药物渗透之间的十二指肠和结肠没有差异。肠道屏障破坏和免疫激活的血浆标志物升高，而与HIV无关，但外周T细胞活化与PLWH单独肠道CD 4 + T细胞的丢失呈负相关。T细胞活化是HIV进展的一个强有力的预测因子，并且独立于血浆病毒载量，这意味着GI CD 4 + T细胞的不可逆损失是南非PLWH的HIV发病机制中的一个关键事件，但潜在的机制仍然未知。
HIV infection in the human gastrointestinal (GI) tract is thought to be central to HIV progression, but knowledge of this interaction is primarily limited to cohorts within Westernized countries. Here, we present a large cohort recruited from high HIV endemic areas in South Africa and found that people living with HIV (PLWH) presented at a younger age for investigation in the GI clinic. We identified severe CD4+ T cell depletion in the GI tract, which was greater in the small intestine than in the large intestine and not correlated with years on antiretroviral treatment (ART) or plasma viremia. HIV-p24 staining showed persistent viral expression, particularly in the colon, despite full suppression of plasma viremia. Quantification of mucosal antiretroviral (ARV) drugs revealed no differences in drug penetration between the duodenum and colon. Plasma markers of gut barrier breakdown and immune activation were elevated irrespective of HIV, but peripheral T cell activation was inversely correlated with loss of gut CD4+ T cells in PLWH alone. T cell activation is a strong predictor of HIV progression and independent of plasma viral load, implying that the irreversible loss of GI CD4+ T cells is a key event in the HIV pathogenesis of PLWH in South Africa, yet the underlying mechanisms remain unknown.
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影响因子：
39
作者：
Freiberg MS;Chang CC;Kuller LH;Skanderson M;Lowy E;Kraemer KL;Butt AA;Bidwell Goetz M;Leaf D;Oursler KA;Rimland D;Rodriguez Barradas M;Brown S;Gibert C;McGinnis K;Crothers K;Sico J;Crane H;Warner A;Gottlieb S;Gottdiener J;Tracy RP;Budoff M;Watson C;Armah KA;Doebler D;Bryant K;Justice AC
通讯作者：
Justice AC
DOI：
10.4049/jimmunol.1001801
发表时间：
2010-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Gordon SN;Cervasi B;Odorizzi P;Silverman R;Aberra F;Ginsberg G;Estes JD;Paiardini M;Frank I;Silvestri G
通讯作者：
Silvestri G
影响因子：
11.1
作者：
Ananworanich, Jintanat;Chomont, Nicolas;Eller, Leigh Ann;Kroon, Eugene;Tovanabutra, Sodsai;Bose, Meera;Nau, Martin;Fletcher, James L. K.;Tipsuk, Somporn;Vandergeeten, Claire;O'Connell, Robert J.;Pinyakorn, Suteeraporn;Michael, Nelson;Phanuphak, Nittaya;Robb, Merlin L.
通讯作者：
Robb, Merlin L.
影响因子：
7.8
作者：
Estes JD;Haase AT;Schacker TW
通讯作者：
Schacker TW
影响因子：
6.4
作者：
Cassol, Edana;Malfeld, Susan;Rossouw, Theresa
通讯作者：
Rossouw, Theresa