HIV infection of human regulatory T cells downregulates Foxp3 expression by increasing DNMT3b levels and DNA methylation in the FOXP3 gene

AIDS

Volumn 27, Issue 13, 2013, Pages 2019-2029

  Pion, Marjorie ^a   Jaramillo Ruiz, Didiana ^a   Martínez, Alberto ^a   Muñoz Fernández, M Angeles ^a   Correa Rocha, Rafael ^a  

^a HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑÓN   (Spain)

Author keywords

DNA methyltransferase; Foxp3; HIV infection; Immune hyperactivation; Methylation; Suppressive function; Treg

Indexed keywords

DNA METHYLTRANSFERASE 3B; INTERLEUKIN 4; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA;

ADULT; ARTICLE; CD4+ T LYMPHOCYTE; CELL CULTURE; CONTROLLED STUDY; CPG ISLAND; CYTOKINE RELEASE; DNA METHYLATION; DOWN REGULATION; FLOW CYTOMETRY; FOXP3 GENE; GENE; GENE EXPRESSION; GENE LOCUS; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IN VITRO STUDY; PHENOTYPE; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE;

ADULT; CYTOKINES; DNA (CYTOSINE-5-)-METHYLTRANSFERASE; DNA METHYLATION; FORKHEAD TRANSCRIPTION FACTORS; GENE EXPRESSION REGULATION; HIV INFECTIONS; HIV-1; HOST-PATHOGEN INTERACTIONS; HUMANS; IMMUNOPHENOTYPING; MALE; T-LYMPHOCYTES, REGULATORY;

EID: 84884482501     PISSN: 02699370     EISSN: 14735571     Source Type: Journal    
DOI: 10.1097/QAD.0b013e32836253fd     Document Type: Article

References (47)

1. Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell 2008; 133:775-787.
2. Tang Q, Bluestone JA. The Foxp3+ regulatory T cell: a jack of all trades, master of regulation. Nat Immunol 2008; 9:239-244.
3. Cvetanovich GL, Hafler DA. Human regulatory T cells in autoimmune diseases. Curr Opin Immunol 2010; 22:753-760.
4. Lund JM, Hsing L, Pham TT, Rudensky AY. Coordination of early protective immunity to viral infection by regulatory T cells. Science 2008; 320:1220-1224.
5. Palomares O, Yaman G, Azkur AK, Akkoc T, Akdis M, Akdis CA. Role of Treg in immune regulation of allergic diseases. Eur J Immunol 2010; 40:1232-1240.
6. Boettler T, Spangenberg HC, Neumann-Haefelin C, Panther E, Urbani S, Ferrari C, et al. T cells with a CD4+CD25+ regulatory phenotype suppress in vitro proliferation of virus-specific CD8+ T cells during chronic hepatitis C virus infection. J Virol 2005; 79:7860-7867.
7. Hazenberg MD, Otto SA, van Benthem BH, Roos MT, Coutinho RA, Lange JM, et al. Persistent immune activation in HIV-1 infection is associated with progression to AIDS. AIDS 2003; 17:1881-1888.
8. Hunt PW, Landay AL, Sinclair E, Martinson JA, Hatano H, Emu B, et al. A low T regulatory cell response may contribute to both viral control and generalized immune activation in HIV controllers. PLoS One 2011; 6:e15924.
9. Eggena MP, Barugahare B, Jones N, Okello M, Mutalya S, Kityo C, et al. Depletion of regulatory T cells in HIV infection is associated with immune activation. J Immunol 2005; 174:4407-4414.
10. Oswald-Richter K, Grill SM, Shariat N, Leelawong M, Sundrud MS, Haas DW, et al. HIV infection of naturally occurring and genetically reprogrammed human regulatory T-cells. PLoS Biol 2004; 2:E198.
11. Prendergast A, Prado JG, Kang YH, Chen F, Riddell LA, Luzzi G, et al. HIV-1 infection is characterized by profound depletion of CD161+ Th17 cells and gradual decline in regulatory T cells. AIDS 2010; 24:491-502.
12. Bi X, Suzuki Y, Gatanaga H, Oka S. High frequency and proliferation of CD4+ FOXP3+ Treg in HIV-1-infected patients with low CD4 counts. Eur J Immunol 2009; 39:301-309.
13. Nilsson J, Boasso A, Velilla PA, Zhang R, Vaccari M, Franchini G, 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.
14. Suchard MS, Mayne E, Green VA, Shalekoff S, Donninger SL, Stevens WS, et al. FOXP3 expression is upregulated in CD4T cells in progressive HIV-1 infection and is a marker of disease severity. PLoS One 2010; 5:e11762.
15. Moreno-Fernandez ME, Zapata W, Blackard JT, Franchini G, Chougnet CA. Human regulatory T cells are targets for human immunodeficiency virus (HIV) infection, and their susceptibility differs depending on the HIV type 1 strain. J Virol 2009; 83:12925-12933.
16. Williams LM, Rudensky AY. Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3. Nat Immunol 2007; 8:277-284.
17. Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, et al. Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 2003; 198:1875-1886.
18. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003; 4:330-336.
19. Allan SE, Crome SQ, Crellin NK, Passerini L, Steiner TS, Bacchetta R, et al. Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. Int Immunol 2007; 19:345-354.
20. Tran DQ, Ramsey H, Shevach EM. Induction of FOXP3 expression in naive human CD4+FOXP3 T cells by T-cell receptor stimulation is transforming growth factor-beta dependent but does not confer a regulatory phenotype. Blood 2007; 110:2983-2990.
21. Huehn J, Polansky JK, Hamann A. Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage? Nat Rev Immunol 2009; 9:83-89.
22. Janson PC, Winerdal ME, Marits P, Thorn M, Ohlsson R, Winqvist O. FOXP3 promoter demethylation reveals the committed Treg population in humans. PLoS One 2008; 3:e1612.
23. Waterhouse PM, Wang MB, Lough T. Gene silencing as an adaptive defence against viruses. Nature 2001; 411:834-842.
24. Kauder SE, Bosque A, Lindqvist A, Planelles V, Verdin E. Epigenetic regulation of HIV-1 latency by cytosine methylation. PLoS Pathog 2009; 5:e1000495.
25. Pion M, Jordan A, Biancotto A, Dequiedt F, Gondois-Rey F, Rondeau S, et al. Transcriptional suppression of in vitro-integrated human immunodeficiency virus type 1 does not correlate with proviral DNA methylation. J Virol 2003; 77:4025-4032.
26. Fang JY, Mikovits JA, Bagni R, Petrow-Sadowski CL, Ruscetti FW. Infection of lymphoid cells by integration-defective human immunodeficiency virus type 1 increases de novo methylation. J Virol 2001; 75:9753-9761.
27. Mikovits JA, Young HA, Vertino P, Issa JP, Pitha PM, Turcoski-Corrales S, et al. Infection with human immunodeficiency virus type 1 upregulates DNA methyltransferase, resulting in de novo methylation of the gamma interferon (IFN-gamma) promoter and subsequent downregulation of IFN-gamma production. Mol Cell Biol 1998; 18:5166-5177.
28. Garcia-Merino I, de Las Cuevas N, Jimenez JL, Gallego J, Gomez C, Prieto C, et al. The Spanish HIV BioBank: a model of cooperative HIV research. Retrovirology 2009; 6:27.
29. Lal G, Zhang N, van der Touw W, Ding Y, Ju W, Bottinger EP, et al. Epigenetic regulation of Foxp3 expression in regulatory T cells by DNA methylation. J Immunol 2009; 182:259-273.
30. Josefowicz SZ, Rudensky A. Control of regulatory T cell lineage commitment and maintenance. Immunity 2009; 30:616-625.
31. Miyara M, Yoshioka Y, Kitoh A, Shima T, Wing K, Niwa A, et al. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 2009; 30:899-911.
32. Garcia JV, Miller AD. Serine phosphorylation-independent downregulation of cell-surface CD4 by nef. Nature 1991; 350:508-511.
33. Hoffmann P, Boeld TJ, Eder R, Huehn J, Floess S, Wieczorek G, et al. Loss of FOXP3 expression in natural human CD4+CD25+ regulatory T cells upon repetitive in vitro stimulation. Eur J Immunol 2009; 39:1088-1097.
34. Kinter A, McNally J, Riggin L, Jackson R, Roby G, Fauci AS. Suppression of HIV-specific T cell activity by lymph node CD25+ regulatory T cells from HIV-infected individuals. Proc Natl Acad Sci U S A 2007; 104:3390-3395.
35. Foxall RB, Albuquerque AS, Soares RS, Baptista AP, Cavaleiro R, Tendeiro R, et al. Memory and naive-like regulatory CD4+ T cells expand during HIV-2 infection in direct association with CD4+ T-cell depletion irrespectively of viremia. AIDS 2011; 25:1961-1970.
36. Card CM, Keynan Y, Lajoie J, Bell CP, Dawood M, Becker M, et al. HIV controllers are distinguished by chemokine expression profile and HIV-specific T-cell proliferative potential. J Acquir Immune Defic Syndr 2012; 59:427-437.
37. Moreno-Fernandez ME, Presicce P, Chougnet CA. Homeostasis and function of regulatory T cells in HIV/SIV infection. J Virol 2012; 86:10262-10269.
38. Presicce P, Orsborn K, King E, Pratt J, Fichtenbaum CJ, Chougnet CA. Frequency of circulating regulatory T cells increases during chronic HIV infection and is largely controlled by highly active antiretroviral therapy. PLoS One 2011; 6:e28118.
39. Del Pozo-Balado Mdel M, Leal M, Mendez-Lagares G, Pacheco YM. CD4(+)CD25(+/hi)CD127(lo) phenotype does not accurately identify regulatory T cells in all populations of HIVinfected persons. J Infect Dis 2010; 201:331-335.
40. Youngblood B, Reich NO. The early expressed HIV-1 genes regulate DNMT1 expression. Epigenetics 2008; 3:149-156.
41. Ji J, Cloyd MW. HIV-1 binding to CD4 on CD4+CD25+ regulatory T cells enhances their suppressive function and induces them to home to, and accumulate in, peripheral and mucosal lymphoid tissues: an additional mechanism of immunosuppression. Int Immunol 2009; 21:283-294.
42. Wan YY, Flavell RA. Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature 2007; 445:766-770.
43. Ouyang W, Beckett O, Ma Q, Li MO. Transforming growth factor-beta signaling curbs thymic negative selection promoting regulatory T cell development. Immunity 2010; 32:642-653.
44. Sugimoto N, Oida T, Hirota K, Nakamura K, Nomura T, Uchiyama T, et al. Foxp3-dependent and -independent molecules specific for CD25+CD4+ natural regulatory T cells revealed by DNA microarray analysis. Int Immunol 2006; 18:1197-1209.
45. Veldman C, Pahl A, Beissert S, Hansen W, Buer J, Dieckmann D, et al. Inhibition of the transcription factor Foxp3 converts desmoglein 3-specific type 1 regulatory T cells into Th2-like cells. J Immunol 2006; 176:3215-3222.
46. Buonaguro L, Tornesello ML, Gallo RC, Marincola FM, Lewis GK, Buonaguro FM. Th2 polarization in peripheral blood mononuclear cells from human immunodeficiency virus (HIV)-infected subjects, as activated by HIV virus-like particles. J Virol 2009; 83:304-313.
47. Arruvito L, Sabatte J, Pandolfi J, Baz P, Billordo LA, Lasala MB, et al. Analysis of suppressor and nonsuppressor FOXP3+T cells in HIV-1-infected patients. PLoS One 2012; 7:e52580.