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CD1d 限制性自然杀伤 T 细胞在印度长期不进展者中得以保留。

CD1d-Restricted Natural Killer T Cells Are Preserved in Indian Long-Term Nonprogressors.

作者信息

Singh Dharmendra, Ghate Manisha, Godbole Sheela, Kulkarni Smita, Thakar Madhuri

机构信息

National AIDS Research Institute, Pune, India.

出版信息

J Acquir Immune Defic Syndr. 2017 Aug 1;75(4):e104-e112. doi: 10.1097/QAI.0000000000001322.

Abstract

BACKGROUND

Natural killer T (NKT) cells act as a bridge between innate and adaptive immune responses. Limited information is available regarding the role of NKT cells in the HIV disease progression especially HIV-1 C infection.

METHODOLOGY

NKT cells were characterized for their frequency and the activation, aging, exhaustion status, and their proliferation ability in 32 long-term nonprogressors (LTNPs), 40 progressors, 18 patients before and after suppressive combination antiretroviral therapy (cART) along with 35 HIV-1-negative subjects using multicolor flow cytometry.

RESULTS

The frequencies of total NKT cells and their subpopulation were significantly higher in LTNPs as compared with those obtained in progressors (P < 0.0001) and were significantly associated with higher CD4 counts and with lower plasma viral loads. The percentage of activated, aged, and exhausted NKT cells were significantly lower in LTNPs as compared with the progressors and inversely correlated with CD4 count and positively with plasma viral loads. The NKT cells from the LTNPs showed higher proliferation ability. The frequency and proliferation ability of the NKT cells were partially restored after 12 months of suppressive cART but still lower than the levels in LTNPs. The degree of restoration after cART was similar in both CD4 and CD4 NKT cells.

CONCLUSION

The findings demonstrate significant association of preserved NKT cells with the nonprogressive HIV infection and also showed that exhausted NKT cells are associated with disease progression. Further characterization of their functionality and assessment of sustenance in HIV infection will help to understand the HIV pathogenesis and to develop immune therapies.

摘要

背景

自然杀伤T(NKT)细胞在先天性和适应性免疫反应之间起桥梁作用。关于NKT细胞在HIV疾病进展尤其是HIV-1 C感染中的作用,目前可用信息有限。

方法

使用多色流式细胞术,对32例长期非进展者(LTNP)、40例进展者、18例接受抑制性联合抗逆转录病毒疗法(cART)前后的患者以及35例HIV-1阴性受试者的NKT细胞进行频率、活化、衰老、耗竭状态及其增殖能力的特征分析。

结果

与进展者相比,LTNP中总NKT细胞及其亚群的频率显著更高(P < 0.0001),并且与更高的CD4细胞计数和更低的血浆病毒载量显著相关。与进展者相比,LTNP中活化、衰老和耗竭的NKT细胞百分比显著更低,并且与CD4细胞计数呈负相关,与血浆病毒载量呈正相关。LTNP的NKT细胞显示出更高的增殖能力。抑制性cART治疗12个月后,NKT细胞的频率和增殖能力部分恢复,但仍低于LTNP中的水平。cART后的恢复程度在CD4和CD4 NKT细胞中相似。

结论

研究结果表明保留的NKT细胞与非进展性HIV感染显著相关,并且还表明耗竭的NKT细胞与疾病进展相关。进一步表征其功能以及评估其在HIV感染中的维持情况,将有助于理解HIV发病机制并开发免疫疗法。

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