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年龄对未接受和接受 cART 的 HIV 感染者 CD4+T 细胞损伤的影响。

Effect of age on the CD4⁺ T-cell impairment in HIV-infected persons without and with cART.

机构信息

*Department of Gastroenterology, Infectious Diseases, and Rheumatology, Medical Clinic I, Campus Benjamin Franklin, Charité-University Medicine Berlin, Berlin, Germany; and †Ärzteforum Seestraβe, Berlin, Germany (Heiko Karcher is now with Ärzteforum Praxis City Ost, Berlin, Germany; Desiree Kunkel is now with Berlin-Brandenburg Center for Regenerative Therapies, Campus Virchow Klinikum, Charité-University Medicine Berlin, Berlin, Germany).

出版信息

J Acquir Immune Defic Syndr. 2014 May 1;66(1):7-15. doi: 10.1097/QAI.0000000000000097.

DOI:10.1097/QAI.0000000000000097
PMID:24378723
Abstract

BACKGROUND

Knowledge about HIV infection in older persons is becoming increasingly important. CD4⁺ T cells are essential for protective immunity, but little is known about the effect of age on the CD4⁺ T-cell impairment in HIV infection.

METHODS

Treatment-naive patients aged older than 50 or younger than 40 years were studied for absolute and relative frequencies of CD31⁺ naive and CD31⁻ naive CD4⁺ T cells, central memory, effector memory, and terminally differentiated CD4⁺ T cells, and compared with age-matched controls. In addition, cellular proliferation and cytokine secretion properties were determined. CD4⁺ T-cell reconstitution was analyzed in older and younger patients with <350 or ≥ 350 CD4⁺ T cells per microliter at initiation of combination antiretroviral therapy (cART).

RESULTS

CD4⁺ T cells of older but not younger HIV-infected patients showed age-inappropriate low levels of CD31⁻ naive cells, increased levels of effector memory cells, and enhanced interferonγ and interleukin-17 secretion. Impaired CD4⁺ T-cell composition persisted in patients who initiated cART at <350 CD4⁺ T cells per microliter. In patients with CD4⁺ T cells ≥ 350 per microliter, alterations were less pronounced and were reversible with cART. Compared with age-matched controls, total CD4⁺ T-cell counts did not differ between treated younger and older HIV-infected patients.

CONCLUSIONS

These data demonstrate that aging enhances the CD4⁺ T-cell impairment in HIV-infected persons mainly by a loss of CD31⁻ naive cells, accumulation of effector memory cells, and increased pro-inflammatory effector functions. Age-related changes in CD4⁺ T-cell composition can be prevented by an early initiation of cART.

摘要

背景

关于老年人中 HIV 感染的知识变得越来越重要。CD4+T 细胞对于保护性免疫至关重要,但对于 HIV 感染中年龄对 CD4+T 细胞损伤的影响知之甚少。

方法

研究了年龄大于 50 岁或小于 40 岁的未经治疗的患者,以比较其与年龄匹配的对照组中 CD31+幼稚和 CD31-幼稚 CD4+T 细胞、中央记忆、效应记忆和终末分化 CD4+T 细胞的绝对和相对频率。此外,还测定了细胞增殖和细胞因子分泌特性。在开始联合抗逆转录病毒治疗(cART)时,分析了 CD4+T 细胞计数<350 个/微升和≥350 个/微升的老年和年轻患者的 CD4+T 细胞重建情况。

结果

与年轻的 HIV 感染者相比,老年 HIV 感染者的 CD4+T 细胞表现出不适当的低水平的 CD31-幼稚细胞、高水平的效应记忆细胞和增强的干扰素γ和白细胞介素-17 分泌。在 CD4+T 细胞计数<350 个/微升的患者开始 cART 时,CD4+T 细胞组成的损伤仍然存在。在 CD4+T 细胞计数≥350 个/微升的患者中,改变不那么明显,并且可以通过 cART 逆转。与年龄匹配的对照组相比,接受治疗的年轻和老年 HIV 感染者的总 CD4+T 细胞计数没有差异。

结论

这些数据表明,衰老主要通过丧失 CD31-幼稚细胞、积累效应记忆细胞和增加促炎效应功能来增强 HIV 感染者的 CD4+T 细胞损伤。通过早期开始 cART,可以预防 CD4+T 细胞组成的与年龄相关的变化。

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