Immune activation and the pathogenesis of HIV disease: Implications for therapy

Journal of HIV Therapy

Volumn 14, Issue 3, 2009, Pages 52-56

  Fernandez, Sonia ^a   Lim, Andrew ^a   French, Martyn ^a,b  

^a UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^b ROYAL PERTH HOSPITAL   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIRETROVIRUS AGENT; CD38 ANTIGEN; CHEMOKINE RECEPTOR CCR5; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; HLA DR ANTIGEN; INTERLEUKIN 6; INTERLEUKIN 8; TRANSCRIPTION FACTOR FOXP3; TUMOR NECROSIS FACTOR ALPHA;

ANTIGEN EXPRESSION; APOPTOSIS; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL METABOLISM; CELL PROLIFERATION; COLOSTRUM; HOMEOSTASIS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE RESPONSE; LYMPHOCYTE DEPLETION; MEMORY CELL; PATHOGENESIS; PHENOTYPE; PROTEIN METABOLISM; REGULATORY T LYMPHOCYTE; REVIEW; SYSTEMIC LUPUS ERYTHEMATOSUS; T LYMPHOCYTE ACTIVATION; UPREGULATION; VIRUS REPLICATION;

ANTI-HIV AGENTS; CD4-POSITIVE T-LYMPHOCYTES; HIV; HIV INFECTIONS; HUMANS; LYMPHOCYTE ACTIVATION; VIRAL LOAD; VIRUS REPLICATION;

EID: 74549154662     PISSN: 14620308     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (75)

1. Brenchley JM, Schacker TW, Ruff LE et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med, 2004, 200, 749-759.
2. Levesque MC, Moody MA, Hwang KK et al. Polyclonal B cell differentiation and loss of gastrointestinal tract germinal centers in the earliest stages of HIV-1 infection. PLoS Med, 2009, 6, e1000107.
3. Mehandru S, PolesMA, Tenner-Racz K et al. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med, 2004, 200, 761-770.
4. Schacker TW, Nguyen PL, Beilman GJ et al. Collagen deposition in HIV-1 infected lymphatic tissues and T cell homeostasis. J Clin Invest, 2002, 110, 1133-1139.
5. Al-Harthi L, Voris J, Becker S et al. Evaluation of the impact of highly active antiretroviral therapy on immune recovery in antiretroviral naïve patients. HIV Med, 2004, 5, 55-65.
6. Benito JM, Lopez M, Lozano S et al. Differential upregulation of CD38 on different T-cell subsets may influence the ability to reconstitute CD4+ T cells under successful highly active antiretroviral therapy. J Acquir Immune Defic Syndr, 2005, 38, 373-381.
7. Connolly NC, Riddler SA, Rinaldo CR. Proinflammatory cytokines in HIV disease: a review and rationale for new therapeutic approaches. AIDS Rev, 2005, 7, 168-180.
8. 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 Infect Dis, 2009, 200, 1212-1215.
9. Hazenberg MD, Cohen Stuart JWT, Otto SA et al. T-cell division in human immunodeficiency virus (HIV)-1 infection is mainly due to immune activation: a longitudinal analysis in patients before and during highly active antiretroviral therapy (HAART). Blood, 2000, 95, 255.
10. Mohri H, Perelson AS, Tung K et al. Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. J Exp Med, 2001, 194, 1277-1287.
11. Giorgi JV, Hultin LE,McKeating JA et al. 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, 859-870.
12. Simmonds P, Beatson D, Cuthbert RJ et al. Determinants of HIV disease progression: six-year longitudinal study in the Edinburgh haemophilia/HIV cohort. Lancet, 1991, 338, 1159-1163.
13. Bofill M, Mocroft A, Lipman M et al. Increased numbers of primed activated CD8+CD38+CD45RO+ T cells predict the decline of CD4+ T cells in HIV-1-infected patients. AIDS, 1996, 10, 827-834.
14. Deeks SG, Kitchen CM, Liu L et al. Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load. Blood, 2004, 104, 942-947.
15. Rodriguez B, Sethi AK, Cheruvu VK et al. Predictive value of plasma HIV RNA level on rate of CD4 T-cell decline in untreated HIV infection. J Am Med Assoc, 2006, 296, 1498-1506.
16. 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.
17. Hunt PW, Martin JN, Sinclair E et al. T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virusinfected patients with sustained viral suppression during antiretroviral therapy. J Infect Dis, 2003, 187, 1534-1543.
18. Landay A, Bettendorf D, Chan E et al. Evidence of immune reconstitution in antiretroviral drug-experienced patients with advanced HIV disease. AIDS Res Hum Retroviruses, 2002, 18, 95-102.
19. Lederman MM, Connick E, Landay A et al. Immunologic responses associated with 12 weeks of combination antiretroviral therapy consisting of zidovudine, lamivudine and ritonavir: results of AIDS Clinical Trials Group Protocol 315. J Infect Dis, 1998, 178, 70-79.
20. Sloand EM, Kumar PN, Kim S et al. Human immunodeficiency virus type 1 protease inhibitor modulates activation of peripheral blood CD4(+) T cells and decreases their susceptibility to apoptosis in vitro and in vivo. Blood, 1999, 94, 1021-1027.
21. Aiuti F, Mezzaroma I. Failure to reconstitute CD4+ T-cells despite suppression of HIV replication under HAART. AIDS Rev, 2006, 8, 88-97.
22. De Milito A, Hejdeman B, Albert J et al. High plasma levels of soluble fas in HIV type 1-infected subjects are not normalized during highly active antiretroviral therapy. AIDS Res Hum Retroviruses, 2000, 16, 1379-1384.
23. Almeida CA, Price P, French MA. Immune activation in patients infected with HIV type 1 and maintaining suppression of viral replication by highly active antiretroviral therapy. AIDS Res Hum Retroviruses, 2002, 18, 1351-1355.
24. Valdez H, Connick E, Smith KY et al. Limited immune restoration after 3 years' suppression of HIV-1 replication in patients with moderately advanced disease. AIDS, 2002, 16, 1859-1866.
25. Anthony KB, Yoder C,Metcalf JA et al. Incomplete CD4 T cell recovery in HIV-1 infection after 12 months of highly active antiretroviral therapy is associated with ongoing increased CD4 T cell activation and turnover. J Acquir Immune Defic Syndr, 2003, 33, 125-133.
26. Mildvan D, Bosch RJ, Kim RS et al. Immunophenotypic markers and antiretroviral therapy (IMART): T cell activation and maturation help predict treatment response. J Infect Dis, 2004, 189, 1811-1820.
27. Fernandez S, Price P, McKinnon EJ et al. Low CD4+ T-cell counts in HIV patients receiving effective antiretroviral therapy are associated with CD4+ T-cell activation and senescence but not with lower effector memory T-cell function. Clin Immunol, 2006, 120, 163-170.
28. Benito JM, Lopez M, Lozano S et al. CD4+ T cell recovery beyond the first year of complete suppression of viral replication during highly active antiretroviral therapy is not influenced by CD8+ T-cell activation. J Infect Dis, 2005, 192, 2142-2146.
29. Benveniste O, Flahault A, Rollot F et al. Mechanisms involved in the low-level regeneration of CD4+ cells in HIV-1 infected patients receiving highly active antiretroviral therapy who have prolonged undetectable plasma viral loads. J Infect Dis, 2005, 191, 1670-1679.
30. Hansjee N, Kaufmann GR, Strub C et al. Persistent apoptosis in HIV- 1-infected individuals receiving potent antiretroviral therapy is associated with poor recovery of CD4 T lymphocytes. J Acquir Immune Defic Syndr, 2004, 36, 671-677.
31. Papagno L, Spina CA,Marchant A et al. Immune activation and CD8+ T-cell differentiation towards senescence in HIV-1 infection. PLOS Biol, 2004, 2, 0173-0185.
32. Sasson SC, Zaunders JJ, Zanetti G et al. Increased plasma interleukin-7 level correlates with decreased CD127 and Increased CD132 extracellular expression on T cell subsets in patients with HIV-1 infection. J Infect Dis, 2006, 193, 505-514.
33. Schacker TW, Brenchley JM, Beilman GJ et al. Lymphatic tissue fibrosis is associated with reduced numbers of naive CD4+ T cells in human immunodeficiency virus type 1 infection. Clin Vaccine Immunol, 2006, 13, 556-560.
34. Andersson J, Fehniger TE, Patterson J et al. Early reduction of immune activation in lymphoid tissue following highly active HIV therapy. AIDS, 1998, 12, 123-129.
35. Bucy RP, Hockett RD, Derdeyn CA et al. Initial increase in blood CD4+ lymphocytes after HIV antiretroviral therapy reflects redistribution from lymphoid tissues. J Clin Invest, 1999, 103, 1391-1398.
36. Boasso A, Vaccari M, Nilsson J et al. Do regulatory T-cells play a role in AIDS pathogenesis? AIDS Rev, 2006, 8, 141-147.
37. Seddiki N, Kelleher AD. Regulatory T cells in HIV infection: who's suppressing what? Curr HIV/AIDS Rep, 2008, 5, 20-26.
38. Sempere JM, Soriano V, Benito JM. T regulatory cells and HIV infection. AIDS Rev, 2007, 9, 54-60.
39. Cao W, Jamieson BD, Hultin LE et al. Regulatory T cell expansion and immune activation during untreated HIV type 1 infection are associated with disease progression. AIDS Res Hum Retroviruses, 2009, 25, 183-191.
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.
41. Montes M, Lewis DE, Sanchez C et al. Foxp3+ regulatory T cells in antiretroviral-naive HIV patients. AIDS, 2006, 20, 1669-1671.
42. 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.
43. Lim A, French MA, Price P. CD4+ and CD8+ T cells expressing FoxP3 in HIV-infected patients are phenotypically distinct and influenced by disease severity and antiretroviral therapy. J Acquir Immune Defic Syndr, 2009, 51, 248-257.
44. 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.
45. Ndhlovu LC, Loo CP, Spotts G et al. FOXP3 expressing CD127lo CD4+ T cells inversely correlate with CD38+ CD8+ T cell activation levels in primary HIV-1 infection. J Leukoc Biol, 2008, 83, 254-262.
46. Rallon NI, Lopez M, Soriano V et al. Level, phenotype and activation status of CD4+FoxP3+ regulatory T cells in patients chronically infected with human immunodeficiency virus and/or hepatitis C virus. Clin Exp Immunol, 2009, 155, 35-43.
47. Allan SE, Crome SQ, Crellin NK et al. Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. Int Immunol, 2007, 19, 345-354.
48. Pillai V, Ortega SB,Wang CK, Karandikar NJ. Transient regulatory Tcells: a state attained by all activated human T-cells. Clin Immunol, 2007, 123, 18-29.
49. Card CM, McLaren PJ,Wachihi C et al. Decreased immune activation in resistance to HIV-1 infection is associated with an elevated frequency of CD4(+)CD25(+)FOXP3(+) regulatory T cells. J Infect Dis, 2009, 199, 1318-1322.
50. Wang R, Kozhaya L, Mercer F et al. Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells. Proc Natl Acad Sci USA, 2009, 106, 13439-13444.
51. Brenchley JM, Price DA, Douek DC. HIV disease: fallout from a mucosal catastrophe. Nat Immunol, 2006, 7, 235-239.
52. Jiang W, Lederman MM, Hunt P et al. Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection. J Infect Dis, 2009, 199, 1177-1185.
53. Brenchley JM, Price DA, Schacker TWet al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med, 2007, 12, 1365-1371.
54. Bourgeois C, Hao Z, Rajewsky K et al. Ablation of thymic export causes accelerated decay of naive CD4 T cells in the periphery because of activation by environmental antigen. Proc Natl Acad Sci USA, 2008, 105, 8691-8696.
55. Herbeuval JP, Boasso A, Grivel JC et al. TNF-related apoptosisinducing ligand (TRAIL) in HIV-1-infected patients and its in vitro production by antigen presenting cells. Blood, 2005, 105, 2458-2464.
56. Herbeuval JP, Grivel JC, Boasso A et al. CD4+ T-cell death induced by infectious and noninfectious HIV-1: role of type 1 interferondependent, TRAIL/DR5-mediated apoptosis. Blood, 2005, 106, 3524-3531.
57. Herbeuval JP, Hardy AW, Boasso A et al. Regulation of TNF-related apoptosis-inducing ligand on primary CD4+ T cells by HIV-1: role of type I IFN-producing plasmacytoid dendritic cells. Proc Natl Acad Sci USA, 2005, 102, 13974-13979.
58. Herbeuval JP, Shearer GM. HIV-1 immunopathogenesis: how good interferon turns bad. Clin Immunol, 2007, 123, 121-128.
59. Mandl JN, Barry AP, Vanderford TH et al. Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections. Nat Med, 2008, 14, 1077-1087.
60. Sedaghat AR, German J, Teslovich TM et al. Chronic CD4+ T-cell activation and depletion in human immunodeficiency virus type 1 infection: type I interferon-mediated disruption of T-cell dynamics. J Virol, 2008, 82, 1870-1883.
61. Baker JV, Duprez D, Rapkin J et al. Untreated HIV infection and large and small artery elasticity. J Acquir Immune Defic Syndr, 2009, 52, 25-31.
62. Palmer S, Maldarelli F, Wiegand A et al. Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc Natl Acad Sci USA, 2008, 105, 3879-3884.
63. Gandhi R, Zheng S, Bosch R et al. Raltegravir (RAL) intensification does not reduce low-level residual viremia in HIV-1-infected patients on antiretroviral therapy (ART): results from ACTG A5244. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Cape Town, South Africa, July 2009. Abstract WELBB1.
64. Lange J, Gazzard B, Diaz R et al. Reduced CD4+ T cell decline and immune activation by NR100157, a specific multi-targeted nutritional intervention, in HIV-1 positive adults not on antiretroviral therapy (BITE). 48th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco, USA, September 2009. Abstract H-1230b.
65. Ronnblom L, Pascual V. The innate immune system in SLE: type I interferons and dendritic cells. Lupus, 2008, 17, 394-399.
66. Haque S, Mirjafari H, Bruce IN. Atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus. Curr Opin Lipidol, 2008, 19, 338-343.
67. Chun TW, Carruth L, Finzi D et al. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature, 1997, 387, 183-188.
68. Douek DC, Brenchley JM, Betts MR et al. HIV preferentially infects HIV-specific CD4+ T cells. Nature, 2002, 417, 95-98.
69. Finkel TH, Tudor-Williams G, Banda NK et al. Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes. Nat Med, 1995, 1, 129-134.
70. D'Orsogna LJ, Krueger RG, McKinnon EJ, French MA. Circulating memory B-cell subpopulations are affected differently by HIV infection and antiretroviral therapy. AIDS, 2007, 21, 1747-1752.
71. Fauci AS, Mavilio D, Kottilil S. NK cells in HIV infection: paradigm for protection or targets for ambush. Nat Rev Immunol, 2005, 5, 835-843.
72. Roederer M, Dubs JG, Anderson MT et al. CD8 naive T cell counts decrease progressively in HIV-infected adults. J Clin Invest, 1995, 95, 2061-2066.
73. Chakrabarti LA, Lewin SR, Zhang L et al. Normal T-cell turnover in sooty mangabeys harboring active simian immunodeficiency virus infection. J Virol, 2000, 74, 1209-1223.
74. Michel P, Balde AT, Roussilhon C et al. Reduced immune activation and T cell apoptosis in human immunodeficiency virus type 2 compared with type 1: correlation of T cell apoptosis with beta2 microglobulin concentration and disease evolution. J Infect Dis, 2000, 181, 64-75.
75. Baenziger S, Heikenwalder M, Johansen P et al. Triggering TLR7 in mice induces immune activation and lymphoid system disruption, resembling HIV-mediated pathology. Blood, 2009, 113, 377-388.