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[抗逆转录病毒治疗后HIV-1感染中T细胞的异常激活]

[Abnormal Activation of T Cells in HIV-1 Infection After Antiretroviral Therapy].

作者信息

Guo Yue, Zhang Yan-Lin, Zhu Dan, Gong Fang-Hong, Gao Yu-Shuang, Zhu Kun-Rong, Li Shan-Shan

机构信息

Department of STD and AIDS Laboratory, Chengdu Center for Disease Control and Prevention, Chengdu 610041, China.

出版信息

Sichuan Da Xue Xue Bao Yi Xue Ban. 2023 Mar;54(2):415-421. doi: 10.12182/20230360208.

Abstract

OBJECTIVE

To investigate the relationship between abnormal activation of T cell subsets in peripheral whole blood and the recovery of immune function in persons infected with HIV-1, and to examine the relationship between the size of the viral reservoir of HIV-1 DNA and T cell subsets.

METHODS

HIV-1-infected persons who underwent routine testing between July 2019 and May 2020 were the target population of the study. According to whether, at the time of enrollment, their CD4 T cells reached 500 cells/μL after antiretroviral therapy (ART), HIV-1-infected persons were divided into two groups, 76 in the deficiency group and 61 in the immune recovery group. In addition, 22 people who were not exposed to HIV-1, and who were tested negative for HIV-1 antibody were selected as the control group. For the three groups of subjects, tests of the T cell subsets were conducted. A total of 77 HIV-1-infected persons, with 44 from the deficiency group and 33 from the recovery group, were examined for HIV-1 DNA reservoir. The deficiency group and the recovery group were followed up 6 months later and the CD4 T cell test results of 133 blood samples were collected, with 74 from the deficiency group and 59 from the recovery group.

RESULTS

The proportions of activated CD4 and CD8 T cells of the deficiency group were higher than those of the recovery group and the control group. The proportions of senescent CD4 and CD8 T cells in the deficiency group were comparable to those of the recovery group, which were higher than those of the control group, showing significant differences only in senescent CD8 T cells, and no significant difference in senescent CD4 T cells. The deficiency group expressed higher levels of effector memory CD4 T and CD8 T cells than the control group did, and the recovery group only expressed a higher level of effect memory CD8 T cells. Both the deficiency group and the recovery group showed lower levels of central memory CD4 T and CD8 T cells than the control group did, and the recovery group had an even lower level of central memory CD4 T cells than the deficiency group did. The recovery group showed a higher expression level of naïve CD4 T cells, and the deficiency group and the recovery group had lower expression levels of naïve CD8 T cells than the control group did. There was no correlation between the size of the viral reservoir of HIV-1 DNA and CD4 T cell count or the T cell subsets. Activated CD4 T cells, activated CD8 T cells, and central memory CD4 T cells were negatively correlated with the follow-up findings for CD4 T cells, with at -0.378, -0.334, and -0.322, respectively ( <0.05). Naïve CD4 T cells and naïve CD8 T cells were positively correlated with the follow-up findings for CD4 T cell subset, with at 0.350 and 0.267, respectively ( <0.05).

CONCLUSION

HIV-1 infected persons have varying degrees of abnormal immune activation of T cell subsets. The abnormal activation of some T-cell subsets is partly associated with the subsequent recovery of immune functions and the size of the viral reservoir of HIV-1 DNA was not associated with the T cell subsets.

摘要

目的

探讨外周全血中T细胞亚群异常激活与HIV-1感染者免疫功能恢复之间的关系,并研究HIV-1 DNA病毒储存库大小与T细胞亚群之间的关系。

方法

2019年7月至2020年5月期间接受常规检测的HIV-1感染者为研究对象。根据入组时接受抗逆转录病毒治疗(ART)后其CD4 T细胞是否达到500个/μL,将HIV-1感染者分为两组,免疫缺陷组76例,免疫恢复组61例。此外,选取22例未接触过HIV-1且HIV-1抗体检测阴性者作为对照组。对三组受试者进行T细胞亚群检测。共对77例HIV-1感染者进行HIV-1 DNA储存库检测,其中免疫缺陷组44例,免疫恢复组33例。对免疫缺陷组和免疫恢复组在6个月后进行随访,收集133份血样的CD4 T细胞检测结果,其中免疫缺陷组74份,免疫恢复组59份。

结果

免疫缺陷组活化CD4和CD8 T细胞比例高于免疫恢复组和对照组。免疫缺陷组衰老CD4和CD8 T细胞比例与免疫恢复组相当,均高于对照组,仅衰老CD8 T细胞有显著差异,衰老CD4 T细胞无显著差异。免疫缺陷组效应记忆CD4 T和CD8 T细胞表达水平高于对照组,免疫恢复组仅效应记忆CD8 T细胞表达水平较高。免疫缺陷组和免疫恢复组中枢记忆CD4 T和CD8 T细胞水平均低于对照组,且免疫恢复组中枢记忆CD4 T细胞水平低于免疫缺陷组。免疫恢复组幼稚CD4 T细胞表达水平较高,免疫缺陷组和免疫恢复组幼稚CD8 T细胞表达水平低于对照组。HIV-1 DNA病毒储存库大小与CD4 T细胞计数或T细胞亚群之间无相关性。活化CD4 T细胞、活化CD8 T细胞和中枢记忆CD4 T细胞与CD4 T细胞随访结果呈负相关,分别为-0.378、-0.334和-0.322(P<0.05)。幼稚CD4 T细胞和幼稚CD8 T细胞与CD4 T细胞亚群随访结果呈正相关,分别为0.350和0.267(P<0.05)。

结论

HIV-1感染者存在不同程度的T细胞亚群免疫激活异常。部分T细胞亚群的异常激活与后续免疫功能恢复部分相关,HIV-1 DNA病毒储存库大小与T细胞亚群无关。

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