CD161+ MAIT cells are severely reduced in peripheral blood and lymph nodes of HIV-infected individuals independently of disease progression.
CD161+ MAIT cells are severely reduced in peripheral blood and lymph nodes of HIV-infected individuals independently of disease progression.
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DOI：
10.1371/journal.pone.0111323
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Schulze zur Wiesch J
中科院分区：
文献类型：
--
作者：
Eberhard JM;Hartjen P;Kummer S;Schmidt RE;Bockhorn M;Lehmann C;Balagopal A;Hauber J;van Lunzen J;Schulze zur Wiesch J
粘膜相关不变T细胞是一种半不变T细胞受体Vα7.2、凝集素受体CD161和IL-18R的联合表达，在肠道抗菌宿主防御中发挥重要作用。目前的研究描述了大量α患者中CD161+MAIT和CD161-TCRV CD7.2+T细胞亚群的特征，重点是疾病进展缓慢的患者和精英控制者。采用多色流式细胞术和酶联免疫吸附试验检测63例患者和26例健康体检者外周血、淋巴结和血浆中单个核细胞的IL-18、sCD14和sCD163水平。此外，在体外用不同的细胞因子和/或固定的E.Coli刺激MAIT细胞进行分析。在HIV感染期间，包括精英控制员在内的所有患者组的血液和淋巴结中都可以检测到CD161+MAIT细胞数量的减少。即使在成功的抗逆转录病毒治疗后，CD161+MAIT细胞数量也没有恢复。CD161+MAIT细胞的缺失与MAIT细胞的高激活水平相关；CD161-TCRVα7.2+T细胞亚群在HIV感染中出现频率增加。在体外用IL-18、IL-12、IL-7和固定的E.Coli刺激MAIT细胞也导致由CD161、IL-18R和CCR6定义的MAIT细胞频率的快速和相加的降低。综上所述，CD161+MAIT细胞亚群不可逆转的减少似乎是HIV感染的早期事件，与疾病的后期无关。这一损失似乎至少部分是由于MAIT细胞在艾滋病毒感染期间对微生物产品和细胞因子的明显刺激具有独特的脆弱性。
Mucosal-associated invariant T (MAIT) cells are characterized by the combined expression of the semi-invariant T cell receptor (TCR) Vα7.2, the lectin receptor CD161, as well as IL-18R, and play an important role in antibacterial host defense of the gut. The current study characterized CD161+ MAIT and CD161–TCRVα7.2+ T cell subsets within a large cohort of HIV patients with emphasis on patients with slow disease progression and elite controllers. Mononuclear cells from blood and lymph node samples as well as plasma from 63 patients and 26 healthy donors were analyzed by multicolor flow cytometry and ELISA for IL-18, sCD14 and sCD163. Additionally, MAIT cells were analyzed after in vitro stimulation with different cytokines and/or fixed E.coli. Reduced numbers of CD161+ MAIT cells during HIV infection were detectable in the blood and lymph nodes of all patient groups, including elite controllers. CD161+ MAIT cell numbers did not recover even after successful antiretroviral treatment. The loss of CD161+ MAIT cells was correlated with higher levels of MAIT cell activation; an increased frequency of the CD161–TCRVα7.2+T cell subset in HIV infection was observed. In vitro stimulation of MAIT cells with IL-18 and IL-12, IL-7 and fixed E.coli also resulted in a rapid and additive reduction of the MAIT cell frequency defined by CD161, IL-18R and CCR6. In summary, the irreversible reduction of the CD161+ MAIT cell subset seems to be an early event in HIV infection that is independent of later stages of the disease. This loss appears to be at least partially due to the distinctive vulnerability of MAIT cells to the pronounced stimulation by microbial products and cytokines during HIV-infection.
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影响因子：
30.5
作者：
Le Bourhis, Lionel;Martin, Emmanuel;Lantz, Olivier
通讯作者：
Lantz, Olivier
影响因子：
6.4
作者：
Krishnan, Sonya;Wilson, Eleanor M. P.;Sereti, Irini
通讯作者：
Sereti, Irini
影响因子：
5.4
作者：
Ahmad, R;Sindhu, STA;Ahmad, A
通讯作者：
Ahmad, A
影响因子：
6.7
作者：
Le Bourhis L;Dusseaux M;Bohineust A;Bessoles S;Martin E;Premel V;Coré M;Sleurs D;Serriari NE;Treiner E;Hivroz C;Sansonetti P;Gougeon ML;Soudais C;Lantz O
通讯作者：
Lantz O
原发性HIV感染中的短期抗逆转录病毒疗法。
DOI：
10.1056/nejmoa1110039
发表时间：
2013-01-17
期刊：
The New England journal of medicine
影响因子：
--
作者：
SPARTAC Trial Investigators;Fidler S;Porter K;Ewings F;Frater J;Ramjee G;Cooper D;Rees H;Fisher M;Schechter M;Kaleebu P;Tambussi G;Kinloch S;Miro JM;Kelleher A;McClure M;Kaye S;Gabriel M;Phillips R;Weber J;Babiker A
通讯作者：
Babiker A