T cell activation is insufficient to drive SIV disease progression.
T cell activation is insufficient to drive SIV disease progression.
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DOI：
10.1172/jci.insight.161111
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发表时间：
2023-07-24
期刊：
影响因子：
8
通讯作者：
Pandrea, Ivona
中科院分区：
文献类型：
--
作者：
Apetrei, Cristian;Gaufin, Thaidra;Brocca-Cofano, Egidio;Sivanandham, Ranjit;Sette, Paola;He, Tianyu;Sivanandham, Sindhuja;Sosa, Natalie Martinez;Martin, Kathryn J.;Raehtz, Kevin D.;Kleinman, Adam J.;Valentine, Audrey;Krampe, Noah;Gautam, Rajeev;Lackner, Andrew A.;Landay, Alan L.;Ribeiro, Ruy M.;Pandrea, Ivona
关键词：
T细胞活化和炎症的消退是非洲绿猴（AGMs）缺乏SIV疾病进展的关键决定因素。虽然经常被认为是一起的，但T细胞激活是对病毒刺激获得性免疫的反应，而炎症反应是对粘膜损伤的先天免疫反应。在早期SIV感染AGMs期间，我们通过Ontak（白细胞介素-2偶联白喉毒素）耗竭调节性T细胞（Treg），将T细胞活化与炎症分离。这种干预消除了T细胞免疫激活的控制，超越了从急性感染到慢性感染的过渡。Ontak对肠道屏障完整性、微生物易位、炎症和高凝没有影响，尽管增加了T细胞活化。Ontak增加了巨噬细胞计数，但降低了它们的激活。持续性T细胞激活影响SIV发病机制，将病毒复制的增加转移到更早的时间点，延长高水平复制，延迟CD4+ T细胞恢复，但在treg耗尽的AGMs中没有任何疾病进展的临床或生物学迹象。因此，通过在不破坏粘膜屏障完整性的情况下诱导T细胞活化，我们发现全身性T细胞活化本身不足以驱动疾病进展，这表明控制全身性炎症（可能通过维持肠道完整性）是siv天然宿主缺乏疾病进展的关键决定因素。
Resolution of T cell activation and inflammation is a key determinant of the lack of SIV disease progression in African green monkeys (AGMs). Although frequently considered together, T cell activation occurs in response to viral stimulation of acquired immunity, while inflammation reflects innate immune responses to mucosal injury. We dissociated T cell activation from inflammation through regulatory T cell (Treg) depletion with Ontak (interleukin-2 coupled with diphtheria toxin) during early SIV infection of AGMs. This intervention abolished control of T cell immune activation beyond the transition from acute to chronic infection. Ontak had no effect on gut barrier integrity, microbial translocation, inflammation, and hypercoagulation, despite increasing T cell activation. Ontak administration increased macrophage counts yet decreased their activation. Persistent T cell activation influenced SIV pathogenesis, shifting the ramp-up in viral replication to earlier time points, prolonging the high levels of replication, and delaying CD4+ T cell restoration yet without any clinical or biological sign of disease progression in Treg-depleted AGMs. Thus, by inducing T cell activation without damaging mucosal barrier integrity, we showed that systemic T cell activation per se is not sufficient to drive disease progression, which suggests that control of systemic inflammation (likely through maintenance of gut integrity) is the key determinant of lack of disease progression in natural hosts of SIVs.
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记忆中的CD4下调CD4+ T细胞体内使非洲绿色猴子具有对进行性Sivagm感染的抗性。
影响因子：
82.9
作者：
通讯作者：
--
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：
6.7
作者：
Estes JD;Harris LD;Klatt NR;Tabb B;Pittaluga S;Paiardini M;Barclay GR;Smedley J;Pung R;Oliveira KM;Hirsch VM;Silvestri G;Douek DC;Miller CJ;Haase AT;Lifson J;Brenchley JM
通讯作者：
Brenchley JM
影响因子：
6.5
作者：
Dander, Erica;Fallati, Alessandra;D'Amico, Giovanna
通讯作者：
D'Amico, Giovanna
影响因子：
6.7
作者：
Favre D;Lederer S;Kanwar B;Ma ZM;Proll S;Kasakow Z;Mold J;Swainson L;Barbour JD;Baskin CR;Palermo R;Pandrea I;Miller CJ;Katze MG;McCune JM
通讯作者：
McCune JM