Generic placeholder image

Current HIV Research

Editor-in-Chief

ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

Research Article

Accelerated Aging of T-Cell Subsets Among ART-Naïve HIV-Infected Chinese Men Who have Sex with Men: A Case-Control Study

Author(s): Li Li, Xing-Wang Li*, Cheng-Jie Ma, Ling-Hang Wang, Feng-Ting Yu, Si-Yuan Yang, Shu-Jing Song and Yun-Xia Tang

Volume 20, Issue 2, 2022

Published on: 14 March, 2022

Page: [129 - 136] Pages: 8

DOI: 10.2174/1570162X20666220216103504

Price: $65

Abstract

Background: Evidence of lymphopoiesis, exhaustion, and premature aging in Chinese patients with human immunodeficiency virus (HIV) is very limited.

Objective: To assess biological aging and immune senescence in Chinese healthy controls (HC) and ART-naïve HIV-infected men who have sex with men (MSM).

Methods: This case-control study was conducted in Beijing Ditan Hospital from March 2018 to June 2019. The percentages of naïve (TN), central memory (TCM), effector memory (TEM), and terminally differentiated memory (TemRA) subsets of CD4 and CD8 T cells were studied, along with markers of senescence (CD28-CD57+) and activation (HLA-DR+). Telomere length of naïve (CD45RA+) and memory (CD45RO+) CD8 T cells were quantified by real-time PCR.

Results: A total of 26 HIV-infected and 20 age-matched HC MSM were included. Compared to the HC group, the CD4/CD8 ratio of the HIV-infected group was significantly reduced (0.30 vs. 1.70, P<0.001); significant differences emerged among all CD8 but not CD4 T cell subsets (all P<0.05). In the HIV-infected group, the percentages of senescent cells (CD28-CD57+) in TN, TCM, TEM, and TemRA subsets of CD8 T cells were higher (all P<0.05); while a significant difference was only found in naïve CD4 T cells (P<0.05). HLA-DR expression was increased significantly in all CD4 and CD8 T cell subsets. Both naïve (CD45RA+) and memory (CD45RO+) CD8 T cells in this population had significantly shorter telomere lengths (P<0.01) compared to the HC group.

Conclusion: HIV-infected MSM exhibit signs of accelerated immune senescence and biological aging, which particularly affects the CD8 T-cell subsets.

Keywords: Immunosenescence, biological aging, telomere, sexual and gender minorities, T-lymphocyte subsets, HIV infections.

Graphical Abstract
[1]
Bhatia R, Ryscavage P, Taiwo B. Accelerated aging and human immunodeficiency virus infection: Emerging challenges of growing older in the era of successful antiretroviral therapy. J Neurovirol 2012; 18(4): 247-55.
[http://dx.doi.org/10.1007/s13365-011-0073-y] [PMID: 22205585]
[2]
Deeks SG. Immune dysfunction, inflammation, and accelerated aging in patients on antiretroviral therapy. Top HIV Med 2009; 17(4): 118-23.
[PMID: 19890183]
[3]
Capeau J. Premature aging and premature age-related comorbidities in HIV-infected patients: Facts and hypotheses. Clin Infect Dis 2011; 53(11): 1127-9.
[http://dx.doi.org/10.1093/cid/cir628] [PMID: 21998279]
[4]
Molina-Pinelo S, Vallejo A, Díaz L, et al. Premature immunosenescence in HIV-infected patients on highly active antiretroviral therapy with low-level CD4 T cell repopulation. J Antimicrob Chemother 2009; 64(3): 579-88.
[http://dx.doi.org/10.1093/jac/dkp248] [PMID: 19608579]
[5]
Desai S, Landay A. Early immune senescence in HIV disease. Curr HIV/AIDS Rep 2010; 7(1): 4-10.
[http://dx.doi.org/10.1007/s11904-009-0038-4] [PMID: 20425052]
[6]
Deeks SG. HIV infection, inflammation, immunosenescence, and aging. Annu Rev Med 2011; 62(1): 141-55.
[http://dx.doi.org/10.1146/annurev-med-042909-093756] [PMID: 21090961]
[7]
Bischof J, Gärtner F, Zeiser K, et al. Immune cells and immunosenescence. Folia Biol (Praha) 2019; 65(2): 53-63.
[PMID: 31464181]
[8]
Appay V, Sauce D. Immune activation and inflammation in HIV-1 infection: Causes and consequences. J Pathol 2008; 214(2): 231-41.
[http://dx.doi.org/10.1002/path.2276] [PMID: 18161758]
[9]
Douek DC, McFarland RD, Keiser PH, et al. Changes in thymic function with age and during the treatment of HIV infection. Nature 1998; 396(6712): 690-5.
[http://dx.doi.org/10.1038/25374] [PMID: 9872319]
[10]
Kelley CF, Kitchen CM, Hunt PW, et al. Incomplete peripheral CD4+ cell count restoration in HIV-infected patients receiving long-term antiretroviral treatment. Clin Infect Dis 2009; 48(6): 787-94.
[http://dx.doi.org/10.1086/597093] [PMID: 19193107]
[11]
Olovnikov AM. Telomeres, telomerase, and aging: Origin of the theory. Exp Gerontol 1996; 31(4): 443-8.
[http://dx.doi.org/10.1016/0531-5565(96)00005-8] [PMID: 9415101]
[12]
Fumagalli M, Rossiello F, Clerici M, et al. Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat Cell Biol 2012; 14(4): 355-65.
[http://dx.doi.org/10.1038/ncb2466] [PMID: 22426077]
[13]
Hewitt G, Jurk D, Marques FD, et al. Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence. Nat Commun 2012; 3(1): 708.
[http://dx.doi.org/10.1038/ncomms1708] [PMID: 22426229]
[14]
Armanios M, Blackburn EH. The telomere syndromes. Nat Rev Genet 2012; 13(10): 693-704.
[http://dx.doi.org/10.1038/nrg3246] [PMID: 22965356]
[15]
Pathai S, Lawn SD, Gilbert CE, et al. Accelerated biological ageing in HIV-infected individuals in South Africa: A case-control study. AIDS 2013; 27(15): 2375-84.
[http://dx.doi.org/10.1097/QAD.0b013e328363bf7f] [PMID: 23751258]
[16]
Srinivasa S, Fitch KV, Petrow E, et al. Soluble CD163 is associated with shortened telomere length in HIV-infected patients. J Acquir Immune Defic Syndr 2014; 67(4): 414-8.
[http://dx.doi.org/10.1097/QAI.0000000000000329] [PMID: 25197827]
[17]
Zanet DL, Thorne A, Singer J, et al. Association between short leukocyte telomere length and HIV infection in a cohort study: No evidence of a relationship with antiretroviral therapy. Clin Infect Dis 2014; 58(9): 1322-32.
[http://dx.doi.org/10.1093/cid/ciu051] [PMID: 24457340]
[18]
Liu JC, Leung JM, Ngan DA, et al. Absolute leukocyte telomere length in HIV-infected and uninfected individuals: Evidence of accelerated cell senescence in HIV-associated chronic obstructive pulmonary disease. PLoS One 2015; 10(4): e0124426.
[http://dx.doi.org/10.1371/journal.pone.0124426] [PMID: 25885433]
[19]
Gonzalez-Serna A, Ajaykumar A, Gadawski I, et al. Rapid decrease in peripheral blood mononucleated cell telomere length after HIV seroconversion, but not HCV seroconversion. J Acquir Immune Defic Syndr 2017; 76(1): e29-32.
[http://dx.doi.org/10.1097/QAI.0000000000001446] [PMID: 28797026]
[20]
Díaz L, Méndez-Lagares G, Correa-Rocha R, et al. Detectable viral load aggravates immunosenescence features of CD8 T-cell subsets in vertically HIV-infected children. J Acquir Immune Defic Syndr 2012; 60(5): 447-54.
[http://dx.doi.org/10.1097/QAI.0b013e318259254f] [PMID: 22549383]
[21]
Gianesin K, Noguera-Julian A, Zanchetta M, et al. Premature aging and immune senescence in HIV-infected children. AIDS 2016; 30(9): 1363-73.
[http://dx.doi.org/10.1097/QAD.0000000000001093] [PMID: 26990630]
[22]
Duffau P, Wittkop L, Lazaro E, et al. Association of immune-activation and senescence markers with non-AIDS-defining comorbidities in HIV-suppressed patients. AIDS 2015; 29(16): 2099-108.
[http://dx.doi.org/10.1097/QAD.0000000000000807] [PMID: 26544576]
[23]
de Martino M, Rossi ME, Azzari C, Gelli MG, Galli L, Vierucci A. Different meaning of CD38 molecule expression on CD4+ and CD8+ cells of children perinatally infected with human immunodeficiency virus type 1 infection surviving longer than five years. Pediatr Res 1998; 43(6): 752-8.
[http://dx.doi.org/10.1203/00006450-199806000-00007] [PMID: 9621984]
[24]
Axelrad MD, Budagov T, Atzmon G. Telomere length and telomerase activity; a Yin and Yang of cell senescence. J Vis Exp 2013; (75): : e50246.
[http://dx.doi.org/10.3791/50246] [PMID: 23728273]
[25]
Deeks SG, Verdin E, McCune JM. Immunosenescence and HIV. Curr Opin Immunol 2012; 24(4): 501-6.
[http://dx.doi.org/10.1016/j.coi.2012.05.004] [PMID: 22658763]
[26]
Wolthers KC, Bea G, Wisman A, et al. T cell telomere length in HIV-1 infection: No evidence for increased CD4+ T cell turnover. Science 1996; 274(5292): 1543-7.
[http://dx.doi.org/10.1126/science.274.5292.1543] [PMID: 8929418]
[27]
Lu W, Mehraj V, Vyboh K, Cao W, Li T, Routy JP. CD4:CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV-positive patients. J Int AIDS Soc 2015; 18(1): 20052.
[http://dx.doi.org/10.7448/IAS.18.1.20052] [PMID: 26130226]
[28]
Méndez-Lagares G, Díaz L, Correa-Rocha R, et al. Specific patterns of CD4-associated immunosenescence in vertically HIV-infected subjects. Clin Microbiol Infect 2013; 19(6): 558-65.
[http://dx.doi.org/10.1111/j.1469-0691.2012.03934.x] [PMID: 22735071]
[29]
Álvarez S, Brañas F, Sánchez-Conde M, Moreno S, López-Bernaldo de Quirós JC, Muñoz-Fernández MÁ. Frailty, markers of immune activation and oxidative stress in HIV infected elderly. PLoS One 2020; 15(3): e0230339.
[http://dx.doi.org/10.1371/journal.pone.0230339] [PMID: 32187205]
[30]
Le Priol Y, Puthier D, Lécureuil C, et al. High cytotoxic and specific migratory potencies of senescent CD8+ CD57+ cells in HIV-infected and uninfected individuals. J Immunol 2006; 177(8): 5145-54.
[http://dx.doi.org/10.4049/jimmunol.177.8.5145] [PMID: 17015699]
[31]
Dion ML, Poulin JF, Bordi R, et al. HIV infection rapidly induces and maintains a substantial suppression of thymocyte proliferation. Immunity 2004; 21(6): 757-68.
[http://dx.doi.org/10.1016/j.immuni.2004.10.013] [PMID: 15589165]
[32]
Fabre-Mersseman V, Dutrieux J, Louise A, et al. CD4+ recent thymic emigrants are infected by HIV in vivo, implication for pathogenesis. AIDS 2011; 25(9): 1153-62.
[http://dx.doi.org/10.1097/QAD.0b013e3283471e89] [PMID: 21505308]
[33]
Lelièvre JD, Melica G, Itti E, et al. Initiation of c-ART in HIV-1 infected patients is associated with a decrease of the metabolic activity of the thymus evaluated using FDG-PET/computed tomography. J Acquir Immune Defic Syndr 2012; 61(1): 56-63.
[http://dx.doi.org/10.1097/QAI.0b013e3182615b62] [PMID: 22706292]
[34]
Brenchley JM, Karandikar NJ, Betts MR, et al. Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells. Blood 2003; 101(7): 2711-20.
[http://dx.doi.org/10.1182/blood-2002-07-2103] [PMID: 12433688]
[35]
Montesano C, Anselmi A, Palma P, et al. HIV replication leads to skewed maturation of CD8-positive T-cell responses in infected children. New Microbiol 2010; 33(4): 303-9.
[PMID: 21213588]
[36]
Yamamoto T, Price DA, Casazza JP, et al. Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection. Blood 2011; 117(18): 4805-15.
[http://dx.doi.org/10.1182/blood-2010-11-317297] [PMID: 21398582]
[37]
Tucker V, Jenkins J, Gilmour J, et al. T-cell telomere length maintained in HIV-infected long-term survivors. HIV Med 2000; 1(2): 116-22.
[http://dx.doi.org/10.1046/j.1468-1293.2000.00010.x] [PMID: 11737334]
[38]
Appay V, Sauce D. Assessing immune aging in HIV-infected patients. Virulence 2017; 8(5): 529-38.
[http://dx.doi.org/10.1080/21505594.2016.1195536] [PMID: 27310730]
[39]
Ouyang Q, Baerlocher G, Vulto I, Lansdorp PM. Telomere length in human natural killer cell subsets. Ann N Y Acad Sci 2007; 1106(1): 240-52.
[http://dx.doi.org/10.1196/annals.1392.001] [PMID: 17303822]
[40]
Weng NP, Granger L, Hodes RJ. Telomere lengthening and telomerase activation during human B cell differentiation. Proc Natl Acad Sci USA 1997; 94(20): 10827-32.
[http://dx.doi.org/10.1073/pnas.94.20.10827] [PMID: 9380719]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy