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慢性人免疫缺陷病毒感染者的免疫激活与免疫重建不全

刘宇超,  李太生

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文章导航 > 协和医学杂志  > 2017 >  8(4-5): 210-214
刘宇超, 李太生. 慢性人免疫缺陷病毒感染者的免疫激活与免疫重建不全[J]. 协和医学杂志, 2017, 8(4-5): 210-214. doi: 10.3969/j.issn.1674-9081.2017.05.004
引用本文: 刘宇超, 李太生. 慢性人免疫缺陷病毒感染者的免疫激活与免疫重建不全[J]. 协和医学杂志, 2017, 8(4-5): 210-214. doi: 10.3969/j.issn.1674-9081.2017.05.004
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Yu-chao LIU, Tai-sheng LI. Immune Activation and Incomplete Immune Reconstitution in Chronic Human Immunodeficiency Virus Infected Patients[J]. Medical Journal of Peking Union Medical College Hospital, 2017, 8(4-5): 210-214. doi: 10.3969/j.issn.1674-9081.2017.05.004
Citation: Yu-chao LIU, Tai-sheng LI. Immune Activation and Incomplete Immune Reconstitution in Chronic Human Immunodeficiency Virus Infected Patients[J]. Medical Journal of Peking Union Medical College Hospital, 2017, 8(4-5): 210-214. doi: 10.3969/j.issn.1674-9081.2017.05.004
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慢性人免疫缺陷病毒感染者的免疫激活与免疫重建不全

doi: 10.3969/j.issn.1674-9081.2017.05.004

  • 中国医学科学院 北京协和医学院 北京协和医院感染内科, 北京 100730

详细信息
    通讯作者:

    李太生  电话:010-69156114, E-mail:litsh@263.net

  • 中图分类号: R453

Immune Activation and Incomplete Immune Reconstitution in Chronic Human Immunodeficiency Virus Infected Patients

  • Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China

More Information
    Corresponding author: LI Tai-sheng  Tel:010-69156114,E-mail:litsh@263.net

    摘要
  • 摘要: 联合抗反转录病毒治疗(combined antiretroviral therapy, cART)问世后, 人免疫缺陷病毒(human immunodeficiency virus, HIV)感染者的生活质量和预期寿命均大大提升, 但仍有少部分慢性感染者在长期cART治疗且病毒完全抑制的情况下, CD4+T细胞不能得到满意的恢复(CD4+T细胞计数 < 500个/μl), 这些免疫重建不全感染者的机会性感染发生率、死亡率远高于免疫重建满意的感染者。免疫重建不全发生的重要机制之一是存在异常的免疫激活。针对HIV感染者免疫激活的干预研究中, 体外实验和临床试验均提示雷公藤多甙可能对慢性HIV感染者免疫激活有抑制作用并对免疫重建不全者的免疫功能起到改善作用。
    Abstract: With the development of combined antiretroviral therapy(cART), the quality of life and life expectancy of the human immunodeficiency virus(HIV) infected adults have been significantly elevated. However, there still remains a small amount of HIV infected adults who could not regain a satisfactory amount of CD4+ T cells(< 500 cells/μl) even with long-term cART treatment and complete viral suppression. These infected individuals with incomplete immune reconstitution are more likely to acquire an opportunistic infection and have a higher mortality rate than infected individuals with complete immune reconstitution. One of the most important mechanisms behind incomplete immune reconstitution is the existence of abnormal immune activation. Among the studies of interventions on immune activation in HIV infected adults, an in vitro experiment and a clinical trial have indicated that Tripterygium wilfordii Hook F(TwHF) could suppress the abnormal immune activation, and may improve the immune reconstitution state in patients with incomplete immune reconstitution.
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    • 参考文献(40)
  • [1] Gaardbo JC, Hartling HJ, Gerstoft J, et al. Incomplete immune recovery in HIV infection:mechanisms, relevance for clinical care, and possible solutions[J]. Clin Dev Immunol, 2012, 2012:670957. https://www.hindawi.com/journals/jir/2012/670957/fig1/
    [2] Autran B, Carcelaint G, Li TS, et al. Restoration of the immune system with anti-retroviral therapy[J]. Immunol Lett, 1999, 66:207-211. doi:  10.1016/S0165-2478(98)00159-X
    [3] Mocroft A, Phillips AN, Gatell J, et al. Normalisation of CD4 counts in patients with HIV-1 infection and maximum virological suppression who are taking combination antiretroviral therapy:an observational cohort study[J]. Lancet, 2007, 370:407-413. doi:  10.1016/S0140-6736(07)60948-9
    [4] Marziali M, De Santis W, Carello R, et al. T-cell homeostasis alteration in HIV-1 infected subjects with low CD4 T-cell count despite undetectable virus load during HAART[J]. AIDS, 2006, 20:2033-2041. doi:  10.1097/01.aids.0000247588.69438.fd
    [5] Erikstrup C, Kronborg G, Lohse N, et al. T-cell dysfunction in HIV-1-infected patients with impaired recovery of CD4 cells despite suppression of viral replication[J]. J Acquir Immune Defic Syndr, 2010, 53:303-310. doi:  10.1097/QAI.0b013e3181ca3f7c
    [6] Marchetti G, Gazzola L, Trabattoni D, et al. Skewed T-cell maturation and function in HIV-infected patients failing CD4+ recovery upon long-term virologically suppressive HAART[J]. AIDS, 2010, 24:1455-1460. doi:  10.1097/QAD.0b013e328339cf40
    [7] Li T, Wu N, Dai Y, et al. Reduced thymic output is a major mechanism of immune reconstitution failure in HIV-infected patients after long-term antiretroviral therapy[J]. Clin Infect Dis, 2011, 53:944-951. doi:  10.1093/cid/cir552
    [8] Engsig FN, Gerstoft J, Kronborg G, et al. Long-term mortality in HIV patients virally suppressed for more than three years with incomplete CD4 recovery:a cohort study[J]. BMC Infect Dis, 2010, 10:318. doi:  10.1186/1471-2334-10-318
    [9] Piketty C, Weiss L, Thomas F, et al. Long-term clinical outcome of human immunodeficiency virus-infected patients with discordant immunologic and virologic responses to a protease inhibitor-containing regimen[J]. J Infect Dis, 2001, 183:1328-1335. doi:  10.1086/319861
    [10] Guihot A, Dentone C, Assoumou L, et al. Residual immune activation in combined antiretroviral therapy-treated patients with maximally suppressed viremia[J]. AIDS, 2016, 30:327-330. doi:  10.1097/QAD.0000000000000815
    [11] French MA, King MS, Tschampa JM, et al. Serum immune activation markers are persistently increased in patients with HIV infection after 6 years of antiretroviral therapy despite suppression of viral replication and reconstitution of CD4+ T cells[J]. J Infect Dis, 2009, 200:1212-1215. doi:  10.1086/605890
    [12] Gandhi RT, McMahon DK, Bosch RJ, et al. Levels of HIV-1 persistence on antiretroviral therapy are not associated with markers of inflammation or activation[J]. PLoS Pathog, 2017, 13:e1006285. https://pubmed.ncbi.nlm.nih.gov/28426825/
    [13] Hunt PW, Brenchley J, Sinclair E, et al. Relationship between T cell activation and CD4+ T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy[J]. J Infect Dis, 2008, 197:126-133. doi:  10.1086/524143
    [14] Noel N, Boufassa F, Lecuroux C, et al. Elevated IP10 levels are associated with immune activation and low CD4(+) T-cell counts in HIV controller patients[J]. AIDS, 2014, 28:467-476. doi:  10.1097/QAD.0000000000000174
    [15] Stiksrud B, Lorvik KB, Kvale D, et al. Plasma IP-10 is increased in immunological nonresponders and associated with activated regulatory T cells and persisting low CD4 counts[J]. J Acquir Immune Defic Syndr, 2016, 73:138-148. doi:  10.1097/QAI.0000000000001080
    [16] Douek DC. Immune activation, HIV persistence, and the cure[J]. Top Antivir Med, 2013, 21:128-132. http://europepmc.org/abstract/MED/24225078
    [17] Hunt PW, Martin JN, Sinclair E, et al. T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy[J]. J Infect Dis, 2003, 187:1534-1543. doi:  10.1086/374786
    [18] Nakanjako D, Ssewanyana I, Mayanja-Kizza H, et al. High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort[J]. BMC Infect Dis, 2011, 11. doi:  10.1186/1471-2334-11-43?site=bmcinfectdis.biomedcentral.com
    [19] Swiecki M, Colonna M. The multifaceted biology of plasmacytoid dendritic cells[J]. Nat Rev Immunol, 2015, 15:471-485. doi:  10.1038/nri3865
    [20] D'Amico R, Yang Y, Mildvan D, et al. Lower CD4+ T lymphocyte nadirs may indicate limited immune reconstitution in HIV-1 infected individuals on potent antiretroviral therapy:analysis of immunophenotypic marker results of AACTG 5067[J]. J Clin Immunol, 2005, 25:106-115. doi:  10.1007/s10875-005-2816-0
    [21] Guo FP, Li YJ, Qiu ZF, et al. Baseline naive CD4+ T-cell level predicting immune reconstitution in treated HIV-infected late presenters[J]. Chin Med J(Engl), 2016, 129:2683-2690. http://pubmedcentralcanada.ca/pmcc/articles/PMC5126159/
    [22] Robbins GK, Spritzler JG, Chan ES, et al. Incomplete reconstitution of T cell subsets on combination antiretroviral therapy in the AIDS Clinical Trials Group protocol 384[J]. Clin Infect Dis, 2009, 48:350-361. doi:  10.1086/595888
    [23] Norris PJ, Zhang J, Worlock A, et al. Systemic Cytokine Levels Do Not Predict CD4(+) T-Cell Recovery After Suppressive Combination Antiretroviral Therapy in Chronic Human Immunodeficiency Virus Infection[J]. Open Forum Infect Dis, 2016, 3:ofw025. doi:  10.1093/ofid/ofw025
    [24] Routy JP, Angel JB, Patel M, et al. Assessment of chloroquine as a modulator of immune activation to improve CD4 recovery in immune nonresponding HIV-infected patients receiving antiretroviral therapy[J]. HIV Med, 2015, 16:48-56. doi:  10.1111/hiv.12171
    [25] Piconi S, Parisotto S, Rizzardini G, et al. Hydroxychloro-quine drastically reduces immune activation in HIV-infected, antiretroviral therapy-treated immunologic nonresponders[J]. Blood, 2011, 118:3263-3272.
    [26] Calza L, Colangeli V, Magistrelli E, et al. Significant decrease in plasma levels of D-dimer, interleukin-8, and interleukin-12 after a 12-month treatment with rosuvastatin in HIV-infected patients under antiretroviral therapy[J]. AIDS Res Hum Retroviruses, 2017, 33:126-132. doi:  10.1089/aid.2016.0134
    [27] Somsouk M, Dunham RM, Cohen M, et al. The immunologic effects of mesalamine in treated HIV-infected individuals with incomplete CD4+ T cell recovery:a randomized crossover trial[J]. PLoS One, 2014, 9:e116306. doi:  10.1371/journal.pone.0116306
    [28] Tenorio AR, Chan ES, Bosch RJ, et al. Rifaximin has a marginal impact on microbial translocation, T-cell activation and inflammation in HIV-positive immune non-responders to antiretroviral therapy-ACTG A5286[J]. J Infect Dis, 2015, 211:780-790. doi:  10.1093/infdis/jiu515
    [29] Rizzardi GP, Lazzarin A, Pantaleo G. Potential role of immune modulation in the effective long-term control of HIV-1 infection[J]. J Biol Regul Homeost Agents, 2002, 16:83-90. http://cn.bing.com/academic/profile?id=c949b73244dfaa39be2e8cadf63b73dd&encoded=0&v=paper_preview&mkt=zh-cn
    [30] Markowitz M, Vaida F, Hare CB, et al. The virologic and immunologic effects of cyclosporine as an adjunct to antiretroviral therapy in patients treated during acute and early HIV-1 infection[J]. J Infect Dis, 2010, 201:1298-1302. doi:  10.1086/651664
    [31] Heredia A, Latinovic O, Gallo RC, et al. Reduction of CCR5 with low-dose rapamycin enhances the antiviral activity of vicriviroc against both sensitive and drug-resistant HIV-1[J]. Proc Natl Acad Sci U S A, 2008, 105:20476-20481. doi:  10.1073/pnas.0810843106
    [32] Bao J, Dai SM. A Chinese herb Tripterygium wilfordii Hook F in the treatment of rheumatoid arthritis:mechanism, efficacy, and safety[J]. Rheumatol Int, 2011, 31:1123-1129. doi:  10.1007/s00296-011-1841-y
    [33] Goldbach-Mansky R, Wilson M, Fleischmann R, et al. Comparison of Tripterygium wilfordii hook F versus sulfasalazine in the treatment of rheumatoid arthritis A randomized trial[J]. Ann Rheum Dis, 2009, 151:229-240. http://europepmc.org/articles/PMC2938780/
    [34] Yu C, Shan T, Feng A, et al. Triptolide ameliorates Crohn's colitis is associated with inhibition of TLRs/NF-kappaB signaling pathway[J]. Fitoterapia, 2011, 82:709-715. doi:  10.1016/j.fitote.2011.02.011
    [35] Liu Q, Chen T, Chen G, et al. Immunosuppressant triptolide inhibits dendritic cell-mediated chemoattraction of neutrophils and T cells through inhibiting Stat3 phosphorylation and NF-kappaB activation[J]. Biochem Biophys Res Commun, 2006, 345:1122-1130. doi:  10.1016/j.bbrc.2006.05.024
    [36] Liu Q. Triptolide and its expanding multiple pharmacological functions[J]. Int Immunopharmacol, 2011, 11:377-383. doi:  10.1016/j.intimp.2011.01.012
    [37] Lv QW, Zhang W, Shi Q, et al. Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of active rheumatoid arthritis(TRIFRA):a randomised, controlled clinical trial[J]. Ann Rheum Dis, 2015, 74:1078-1086. doi:  10.1136/annrheumdis-2013-204807
    [38] 徐伯扬.雷公藤甲素、雷公藤红素对外周血单个核细胞干扰素刺激基因表达的影响[D].北京协和医学院, 2014.
    [39] Li T, Xie J, Li Y, et al. Tripterygium wilfordii Hook F extract in cART-treated HIV patients with poor immune response:a pilot study to assess its immunomodulatory effects and safety[J]. HIV Clin Trials, 2015, 16:49-56. doi:  10.1179/1528433614Z.0000000005
    [40] 孙蒙清.雷公藤多甙对艾滋病免疫重建不全患者的干预研究[D].北京协和医学院, 2013.
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  • 收稿日期:  2017-06-23
  • 刊出日期:  2017-09-30

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