Regulatory T cells in HIV-infected immunological nonresponders are increased in blood but depleted in lymphoid tissue and predict immunological reconstitution

Journal of Acquired Immune Deficiency Syndromes

Volumn 66, Issue 4, 2014, Pages 349-357

  Gaardbo, Julie C ^a   Hartling, Hans J ^a   Ronit, Andreas ^a   Springborg, Karoline ^a   Gjerdrum, Lise M R ^a   Ralfkiær, Elisabeth ^a   Thorsteinsson, Kristina ^b   Ullum, Henrik ^a   Andersen, Åse B ^c   Nielsen, Susanne D ^a  

^a University of Copenhagen   (Denmark)

^b HVIDOVRE HOSPITAL   (Denmark)

^c UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

INTERLEUKIN 10; TRANSCRIPTION FACTOR FOXP3;

ADULT; ANTIBODY LABELING; ARTICLE; BLOOD; CD4 LYMPHOCYTE COUNT; CONTROLLED STUDY; CYTOKINE PRODUCTION; FEMALE; FLOW CYTOMETRY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INTERNATIONAL NORMALIZED RATIO; LYMPHOID TISSUE; MALE; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE SUBPOPULATION;

ADULT; AGED; ANTI-HIV AGENTS; CASE-CONTROL STUDIES; CD4 LYMPHOCYTE COUNT; FEMALE; FORKHEAD TRANSCRIPTION FACTORS; GENE EXPRESSION REGULATION; HIV INFECTIONS; HUMANS; INTERLEUKIN-10; LYMPHOID TISSUE; MALE; MIDDLE AGED; T-LYMPHOCYTES, REGULATORY;

EID: 84903771869     PISSN: 15254135     EISSN: 10779450     Source Type: Journal    
DOI: 10.1097/QAI.0000000000000173     Document Type: Article

References (41)

1. Piketty C, Castiel P, Belec L, et al. Discrepant responses to triple combination antiretroviral therapy in advanced HIV disease. AIDS. 1998;12: 745-750. (Pubitemid 28190697)
2. Autran B, Carcelaint G, Li TS, et al. Restoration of the immune system with anti-retroviral therapy. Immunol Lett. 1999;66:207-211. (Pubitemid 29136840)
3. Autran B, Carcelain G, Li TS, et al. Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science. 1997;277:112-116. (Pubitemid 27450659)
4. 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 Clin Immunol. 2005;25:106-115
5. Kaufmann GR, Furrer H, Ledergerber B, et al. Characteristics, determinants, and clinical relevance of CD4 T cell recovery to, 500 cells/microL in HIV type 1-infected individuals receiving potent antiretroviral therapy. Clin Infect Dis. 2005;41:361-372. (Pubitemid 41022115)
6. Moore RD, Keruly JC. CD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppression. Clin Infect Dis. 2007;44:441-446. (Pubitemid 46147630)
7. 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. BMC Infect Dis. 2010;10:318
8. Greub G, Ledergerber B, Battegay M, et al. Clinical progression, survival, and immune recovery during antiretroviral therapy in patients with HIV-1 and hepatitis C virus coinfection: the Swiss HIV Cohort Study. Lancet. 2000;356:1800-1805
9. Sabin CA, Smith CJ, d'Arminio MA, et al. Response to combination antiretroviral therapy: variation by age. AIDS. 2008;22:1463-1473
10. Gaardbo JC, Hartling HJ, Gerstoft J, et al. Incomplete immune recovery in HIV infection: mechanisms, relevance for clinical care, and possible solutions. Clin Dev Immunol. 2012;2012:670957
11. von BH. Mechanisms of suppression by suppressor T cells. Nat Immunol. 2005;6:338-344
12. Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol. 2005;6:345-352. (Pubitemid 41716771)
13. Hazenberg MD, Otto SA, van Benthem BH, et al. Persistent immune activation in HIV-1 infection is associated with progression to AIDS. AIDS. 2003;17:1881-1888. (Pubitemid 37070273)
14. Gaardbo JC, Nielsen SD, Vedel SJ, et al. Regulatory T cells in human immunodeficiency virus-infected patients are elevated and independent of immunological and virological status, as well as initiation of highly active anti-retroviral therapy. Clin Exp Immunol. 2008;154:80-86
15. Weiss L, Donkova-Petrini V, Caccavelli L, et al. Human immunodeficiency virus-driven expansion of CD4+CD25+ regulatory T cells, which suppress HIV-specific CD4 T-cell responses in HIV-infected patients. Blood. 2004;104:3249-3256. (Pubitemid 39507143)
16. Lim A, Tan D, Price P, et al. Proportions of circulating T cells with a regulatory cell phenotype increase with HIV-associated immune activation and remain high on antiretroviral therapy. AIDS. 2007;21: 1525-1534. (Pubitemid 47075472)
17. Kanwar B, Favre D, McCune JM. Th17 and regulatory T cells: implications for AIDS pathogenesis. Curr Opin HIV AIDS. 2010;5:151-157
18. Kolte L, Gaardbo JC, Skogstrand K, et al. Increased levels of regulatory T cells (Tregs) in human immunodeficiency virus-infected patients after 5 years of highly active anti-retroviral therapy may be due to increased thymic production of naive Tregs. Clin Exp Immunol. 2009;155:44-52
19. Epple HJ, Loddenkemper C, Kunkel D, et al. Mucosal but not peripheral FOXP3+ regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART. Blood. 2006;108: 3072-3078
20. Shaw JM, Hunt PW, Critchfield JW, et al. Increased frequency of regulatory T cells accompanies increased immune activation in rectal mucosae of HIV-positive noncontrollers. J Virol. 2011;85:11422-11434
21. Angin M, Kwon DS, Streeck H, et al. Preserved function of regulatory T cells in chronic HIV-1 infection despite decreased numbers in blood and tissue. J Infect Dis. 2012;205:1495-1500
22. Miyara M, Yoshioka Y, Kitoh A, et al. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity. 2009;30:899-911
23. 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 Infect Dis. 2001;183:1328-1335 (Pubitemid 32337114)
24. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet. 2008;372:293-299
25. Gaardbo JC, Hartling HJ, Thorsteinsson K, et al. CD3+CD8+CD161high Tc17 cells are depleted in HIV-infection. AIDS. 2013;27:659-662
26. Gaardbo JC, Ronit A, Hartling HJ, et al. Immunoregulatory T cells may be involved in preserving CD4 T cell counts in HIV-infected long-term nonprogressors and controllers. J Acquir Immune Defic Syndr. 2014;65: 10-18
27. Kolte L, Gaardbo JC, Karlsson I, et al. Dysregulation of CD4+CD25 +CD127lowFOXP3+ regulatory T cells in HIV-infected pregnant women. Blood. 2011;117:1861-1868
28. Hartling HJ, Gaardbo JC, Ronit A, et al. CD4(+) and CD8(+) regulatory t cells (Tregs) are elevated and Display an active phenotype in patients with chronic HCV Mono-infection and HIV/HCV co-infection. Scand J Immunol. 2012;76:294-305
29. Gjerdrum LM, Woetmann A, Odum N, et al. FOXP3+ regulatory T cells in cutaneous T-cell lymphomas: association with disease stage and survival. Leukemia. 2007;21:2512-2518. (Pubitemid 350148895)
30. 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. AIDS. 2006;20:2033-2041. (Pubitemid 44611056)
31. 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 Acquir Immune Defic Syndr. 2010;53:303-310
32. Marchetti G, Gazzola L, Trabattoni D, et al. Skewed T-cell maturation and function in HIV-infected patients failing CD4+ recovery upon longterm virologically suppressive HAART. AIDS. 2010;24:1455-1460
33. 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. Clin Infect Dis. 2011;53:944-951
34. Lewden C, Chene G, Morlat P, et al. HIV-infected adults with a CD4 cell count greater than 500 cells/mm3 on long-term combination antiretroviral therapy reach same mortality rates as the general population. J Acquir Immune Defic Syndr. 2007;46:72-77. (Pubitemid 47514615)
35. Lewden C, Bouteloup V, De WS, et al. All-cause mortality in treated HIV-infected adults with CD4 ./=500/mm3 compared with the general population: evidence from a large European observational cohort collaboration. Int J Epidemiol. 2012;41:433-445
36. Rueda CM, Velilla PA, Chougnet CA, et al. Incomplete normalization of regulatory t-cell frequency in the gut mucosa of Colombian HIV-infected patients receiving long-term antiretroviral treatment. PLoS One. 2013;8: e71062
37. Horta A, Nobrega C, Amorim-Machado P, et al. Poor immune reconstitution in HIV-infected patients associates with high percentage of regulatory CD4+ T cells. PLoS One. 2013;8:e57336
38. Mendez-Lagares G, del Pozo Balado MM, Genebat GM, et al. Severe immune dysregulation affects CD4(+)CD25(hi)FoxP3(+) regulatory T cells in HIV-infected patients with low-level CD4 T-cell repopulation despite suppressive highly active antiretroviral therapy. J Infect Dis. 2012;205:1501-1509
39. Nilsson J, Boasso A, Velilla PA, et al. HIV-1-driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS. Blood. 2006;108:3808-3817. (Pubitemid 44864563)
40. Eggena MP, Barugahare B, Jones N, et al. Depletion of regulatory T cells in HIV infection is associated with immune activation. J Immunol. 2005; 174:4407-4414. (Pubitemid 40396024)
41. Simonetta F, Lecuroux C, Girault I, et al. Early and long-lasting alteration of effector CD45RA(-)Foxp3(high) regulatory T-cell homeostasis during HIV infection. J Infect Dis. 2012;205:1510-1519