Causes of T lymphocyte activation in HIV-infected patients coinfected with hepatitis C virus


Aim. To establish the causes of T lymphocyte activation in human immunodeficiency virus (HIV)-infected patients coinfected with hepatitis C (HCV) who are adherent to their antiretroviral therapy regimen and interferon untreated. Subjects and methods. Examinations were made in 62 people who were HIV+HCV-positive (n=21), HIV+HCV-negative (n=21), and noninfected volunteers (n=20). The activation (CD38+HLA-DR+) and proliferation (Ki-67+) of CD4+ and CD8+ T lymphocytes were estimated. The blood concentration of intestinal fatty acid-binding protein (I-FABP) was determined. Results. The proportion of activated cells among the CD4+ T lymphocytes was equal in the HIV+HCV-positive and HIV+HCV-negative groups. But these indicators were statistically significantly higher than those in the controls (HIV- HCV-). CD8+ T cell activation was greater in the HIV/HCV-coinfected patients than that in the other groups and that was higher in the HIV monoinfected than in the noninfected. The blood I-FABP concentrations were elevated in the HIV+HCV-positive and HIV+HCV groups compared with those in the HIV-HCV-negative group, but these did not differ among themselves. In the HIV+HCV-negative patients, CD4+ and CD8+ T cell activation directly and statistically significantly correlated with blood I-FABP levels. In the HIV+HCV-positive group, this correlation remained only for CD4+ T lymphocytes. CD8+ T cell activation in HIV/HCV-coinfected patients was unrelated to I-FABP concentrations. Conclusion. The increased activation of CD4+ and CD8+ T lymphocytes in HIV monoinfection was found to be associated with intestinal epithelial destruction and unrelated to cell division processes. In HIV/HCV coinfection, the activated state of CD4+ T cells is determined by both the level of proliferative processes and impairment of the intestinal barrier and that of CD8+ T cells is only by proliferation.


  1. Giorgi JV, Hultin LE, McKeating JA, Johnson TD, Owens B, Jacobson LP, Shih R, Lewis J, Wiley DJ, Phair JP, Wolinsky SM, Detels R. Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. J Infect Dis. 1999;179(4):859-870. doi: 10.1086/314660
  2. Paiardini M, Müller-Trutwin M. HIV-associated chronic immune activation. Immunol Rev. 2013;254(1):78-101. doi: 10.1111/imr.12079
  3. Catalfamo M, Wilhelm C, Tcheung L, Proschan M, Friesen T, Park JH, Adelsberger J, Baseler M, Maldarelli F, Davey R, Roby G, Rehm C, Lane C. CD4 and CD8 T Cell Immune Activation during Chronic HIV Infection: Roles of Homeostasis, HIV, Type I IFN, and IL-7. J Immunol. 2011;186(4):2106-2116. doi: 10.4049/jimmunol.1002000
  4. Brenchley JM, Paiardini M, Knox KS, Asher AI, Cervasi B, Asher TE, Scheinberg P, Price DA, Hage CA, Kholi LM, Khoruts A, Frank I, Else J, Schacker T, Silvestri G, Douek DC. Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood. 2008;112(7):2826-2835. doi: 10.1182/blood-2008-05-159301
  5. Butler SL, Valdez H, Westby M, Perros M, June CH, Jacobson JM, Levy Y, Cooper DA, Douek D, Lederman MM, Tebas P. Disease-modifying therapeutic concepts for HIV in the era of highly active antiretroviral therapy. JAIDS. 2011;58(3):297-303. doi: 10.1097/qai.0b013e31822ccfcc
  6. Catalfamo M, Di Mascio M, Hu Z, Srinivasula S, Thaker V, Adelsberger J, Rupert A, Baseler M, Tagaya Y, Roby G, Rehm C, Follmann D, Lane HC. HIV infection-associated immune activation occurs by two distinct pathways that differentially affect CD4 and CD8 T cells. PNAS. 2008;105(50):19851-19856. doi: 10.1073/pnas.0810032105
  7. Kozlov AP, Shaboltas AV, Toussova OV, Verevochkin SV, Masse BR, Perdue T, Beauchamp G, Sheldon W, Miller WC, Heimer R, Ryder RW, Hoffman IF. HIV incidence and factors associated with HIV acquisition among injection drug users in St Petersburg, Russia. AIDS. 2006;20(6):901-906. doi: 10.1097/01.aids.0000218555.36661.9c
  8. Rhodes T, Platt L, Judd A, Mikhailova LA, Sarang A, Wallis N, Alpatova T, Hickman M, Parry JV. Hepatitis C virus infection, HIV co-infection, and associated risk among injecting drug users in Toliatti, Russia. Int J STD AIDS. 2005;16(11):749-754. doi: 10.1258/095646205774763180
  9. Sandberg JK, Falconer K, Gonzalez VD. Chronic immune activation in the T cell compartment of HCV/HIV-1 co-infected patients. Virulence. 2010;1(3):177-179. doi: 10.4161/viru.1.3.11206
  10. Brenchley J, Price D, Douek D. HIV disease: fallout from a mucosal catastrophe? Nature Immunology. 2006;7(3):235-239. doi: 10.1038/ni1316
  11. Avettand-Fènoël V, Boufassa F, Galimand J, Meyer L, Rouzioux C. HIV-1 DNA for the measurement of the HIV reservoir is predictive of disease progression in seroconverters whatever the mode of result expression is. J Clin Virol. 2008;42(4):399-404. doi: 10.1016/j.jcv.2008.03.013
  12. Weiss L, Chevalier M, Assoumou L et al. T-cell activation positively correlates with cell-associated HIV-DNA level in viremic patients with primary or chronic HIV-1 infection. AIDS. 2014;28(11):1683-1687. doi: 10.1097/qad.0000000000000319
  13. Hofer U, Speck R. Disturbance of the gut-associated lymphoid tissue is associated with disease progression in chronic HIV infection. Semin Immunopathol. 2009;31(2):257-266. doi: 10.1007/s00281-009-0158-3
  14. Mehandru S, Poles M, Tenner-Racz K, Jean-Pierre P, Manuelli V, Lopez P, Shet A, Low A, Mohri H, Boden D, Racz P, Markowitz M. Lack of mucosal immune reconstitution during prolonged treatment of acute and early HIV-1 infection. PLoS Med. 2006;3(12):e484. doi: 10.1371/journal.pmed.0030484
  15. Guadalupe M, Sankaran S, George M Reay E, Verhoeven D, Shacklett BL, Flamm J, Wegelin J, Prindiville T, Dandekar S. Viral suppression and immune restoration in the gastrointestinal mucosa of human immunodeficiency virus type 1-infected patients initiating therapy during primary or chronic infection. J Virol. 2006;80(16):8236-8247. doi: 10.1128/jvi.00120-06
  16. Page E, Greathead L, Metcalf R, Clark SA, Hart M, Fuchs D, Pantelidis P, Gotch F, Pozniak A, Nelson M, Boasso A, Gazzard B, Kelleher P. Loss of Th22 cells is associated with increased immune activation and IDO-1 activity in HIV-1 infection. JAIDS. 2014;67(3):227-235. doi: 10.1097/qai.0000000000000294
  17. Klatt N, Funderburg N, Brenchley J. Microbial translocation, immune activation, and HIV disease. Trends Microbiol. 2013;21(1):6-13. doi: 10.1016/j.tim.2012.09.001
  18. Kovacs JA, Lempicki RA, Sidorov IA, Adelsberger JW, Herpin B, Metcalf JA, Sereti I, Polis MA, Davey RT, Tavel J, Falloon J, Stevens R, Lambert L, Dewar R, Schwartzentruber DJ, Anver MR, Baseler MW, Masur H, Dimitrov DS, Lane HC. Identification of dynamically distinct subpopulations of T lymphocytes that are differentially affected by HIV. J Exp Med. 2001;194(12):1731-1741. doi: 10.1084/jem.194.12.1731

Copyright (c) 2016 Shmagel K.V., Shmagel N.G., Korolevskaya L.B., Saydakova E.V., Chereshnev V.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Address of the Editorial Office:

  • Novij Zykovskij proezd, 3, 40, Moscow, 125167

Correspondence address:

  • Alabyan Street, 13/1, Moscow, 127055, Russian Federation

Managing Editor:

  • Tel.: +7 (926) 905-41-26
  • E-mail:


© 2018-2021 "Consilium Medicum" Publishing house

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies