Activación inmunológica crónica en la patogénesis de la enfermedad por virus de inmunodeficiencia humana

Autores/as

  • Henry Chinhong Chan Cheng Universidad de Costa Rica
  • Silvia Leticia Monge Rodríguez Universidad de Costa Rica
  • María del Rosario Espinoza Mora Universidad de Costa Rica

DOI:

https://doi.org/10.51481/amc.v59i1.947

Palabras clave:

VIH, activación inmunológica, inflamación crónica, inmunidad virus-específica

Resumen

Justificación y objetivo: el virus de inmunodeficiencia humana induce una activación inmune crónica que lleva a la progresión de la enfermedad por VIH. Estudios en primates han demostrado que el desarrollo de una infección retroviral patológica está determinada tanto por la respuesta del sistema inmunitario al virus, como por sus propiedades citopáticas. Esta revisión pretende resumir los conocimientos actuales acerca de los principales mecanismos envueltos en la activación inmune crónica durante la infección por VIH y sus repercusiones en la inmunidad virus-específica.

Metodología: las referencias bibliográficas se obtuvieron en la base de datos PubMed. Se incluyeron todos los artículos publicados en lengua inglesa entre 1990 y 2016, hallados bajo las palabras clave “immunopathology and hiv“ e “immune activation and hiv“.

Revisión: se discute la influencia de la inflamación persistente sobre el establecimiento de la enfermedad por VIH y la generación de condiciones patológicas no relacionadas con la infección. Tratamientos dirigidos a modular la inflamación podrían retardar el progreso de la enfermedad y reducir los daños colaterales de la estimulación inmunológica inducida por VIH.

Conclusión: la evidencia parece indicar que la activación inmune crónica es la principal causa de la depleción de células T CD4+, la pérdida de inmunidad específica contra el virus y el establecimiento de enfermedades no relacionadas directamente con la infección viral en pacientes que reciben terapia antiretroviral.

 

Citas

Fauci AS, Pantaleo G, Stanley S, Weissman D. Immunopathogenic mechanisms of HIV infection. Ann Intern Med 1996;124:654–63

Doitsh G, Cavrois M, Lassen KG, Zepeda O, Yang Z, Santiago ML, et al. Abortive HIV infection mediates CD4 T cell depletion and inflammation in human lymphoid tissue. Cell 2010;143(5):789–801

Cooper A, Garcia M, Petrovas C, Yamamoto T, Koup RA, Nabel GJ. HIV-1 causes CD4 cell death through DNA-dependent proteinkinase during viral integration. Nature 2013;498(7454):376–9

Finkel TH, Tudor-Williams G, Banda NK, Cotton MF, Curiel T, Monks C et al. Apoptosis occurs predominantly in bystander cells and not in pro- ductively infected cells of HIV- and SIV-infected lymphnodes. Nat Med 1995;1:129–34

Draenert R, Verrill CL, Tang Y, Allen TM, Wurcel AG, Boczanowski M et al. Persistent recognition of autologous virus by high-avidity CD8 T cells in chronic, progressive human immunodeficiency virus type1 infection. J Virol 2004;78(2):630–41

Hellerstein MK, Hoh RA, Hanley MB, Cesar D, Lee D, Neese RA, et al. Subpopulations of long lived and short lived T cells in advanced HIV-1 infection. J Clin Invest 2003;112(6):956–66

Hazenberg MD, Stuart JW, Otto SA, Borleffs JC, Boucher CA, de Boer RJ, et al. T cell division in human immunodeficiency virus (HIV-1)-infection is mainly due to immuneactivation: a longitudinal analysis in patients before and during highly active antiretroviral therapy. Blood 2000;95(1):249–55

Mohri H, Perelson AS, Tung K, Ribeiro RM, Ramratnam B, Markowitz M, et al. Increased turnover of T lymphocytesin HIV- 1 infection and its reduction by antiretroviral therapy. J Exp Med 2001;194:1277–87

Lempicki RA, Kovacs JA, Baseler MW, Adelsberger JW, Dewar RL, Natarajan V, et al. Impact of HIV-1 infection and highly active antiretroviral therapy on the kinetics of CD4+ and CD8+ T cell turnover in HIV-infected patients. Proc Natl Acad Sci USA 2000;97:13778–83

von Sydow M, Sonnerborg A, Gaines H, Strannegard O. Interferon-alpha and tumor necrosis factor-alpha in serum of patients in various stages of HIV-1 infection. AIDS ResHum Retroviruses 1991;7:375–80

Bofill M, Mocroft A, Lipman M, Medina E, Borthwick NJ, Sabin CA, et al. Increased numbers of primed activated CD8+CD38+CD45RO+ T cells predict the decline of CD4+ T cells in HIV-1-infectedpatients. AIDS 1996;10:827–34

Giorgi JV, Hultin LE, Mc Keating JA, Johnson TD, Owens B, Jacobson LP, et al. Shorter survival in advanced Human Immunodeficiency virus type 1 infec- tion is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. J Infect Dis 1999;179:859–70

Sousa AE, Carneiro J, Meier-Schellersheim M, Grossman Z, Victorino RM. CD4 T cell depletion is linked directly to immune activation in the pathogenesis of HIV-1 and HIV-2 but only indirectly to the viral load. J Immunol 2002;169:3400–6.

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;17:1881–8

Marlink R, Kanki P, Thior I, Travers K, Eisen G, Siby T, et al. Reduced rate of disease development after HIV-2 infection as compared to HIV-1. Science 1994;265:1587–90

Schramm B, Penn ML, Palacios EH, Grant RM, Kirchhoff F, Goldsmith MA. Cytopathicity of human immunodeficiency virus type2 (HIV-2) in human lymphoid tissue is coreceptor dependent and comparable to that of HIV-1. J Virol 2000;74:9594–600

Grossman Z, Meier-Schellersheim M, Sousa AE, Victorino RMM, Paul WE. CD4 T-cell depletion in HIV infection: are we closer to understanding the cause? Nat Med 2002;8:319–23

Jansen CA, van Baarle D, Miedema F. HIV-specific CD4+ T cells and viremia: who’s in control? Trends Immunol 2006;27:119–24

Deeks SG. HIV infection, inflammation, immunosenescence and aging. Annu Rev Med 2011;62:141–55

Beignon AS, McKenna K, Skoberne M, Manches O, Da Silva I, Kavanagh DG, et al. Endocytosis of HIV-1 activates plasmacytoid dendritic cells via toll like receptor viral RNA interactions. J Clin Invest 2005;115(11):3265–75

Meier A, Alter G, Frahm N, Sidhu H, Li B, Bagchi A, et al. MyD88-dependent immune activation mediated by human immunodeficiency virus type 1- encoded toll-like receptor ligands. J Virol 2007;81:8180–91

Ito T, Kanzler H, Duramad O, Cao W, Liu YJ. Specialization, kinetics, and repertoire of type 1 interferon responses by human plasmacytoid predendritic cells. Blood 2006;107:2423–31

Manches O, Frleta D, Bhardwaj N. Dendritic cells in progression and pathology of HIV infection. Trends Immunol 2013;35(3):114-22

Alter G, Suscovich TJ, Teigen N, Meier A, Streeck H, Brander C, et al. Singlestranded RNA derived from HIV-1 serves as a potent activator of NK cells. J Immunol 2007;178:7658–66

Sedaghat AR, German J, Teslovich TM, Cofrancesco JJr, Jie CC, Talbot CCJr, 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;82:1870–83

Wolf K, Tsakiris DA, Weber R, Erb P, Battegay M. Antiretroviral therapy reduces markers of endothelial and coagulation activation in patients infected with human immunodeficiency virus type 1. J Infect Dis 2002;185:456–62

Theofilopoulos AN, Baccala R, Beutler B, Kono DH. Type I interferons (alpha/ beta) in immunity and autoimmunity. Annu Rev Immunol 2005;23:307–36

Hardy GA, Sieg S, Rodriguez B, Anthony D, Asaad R, Jiang W, et al. Interferonalpha is the primary plasma type-I IFN in HIV-1 infection and correlates with immuneactivation and disease markers. PLoS One 2013;8: e56527

Chang J, Lindsay RJ, Kulkarni S, Lifson JD, Carrington M, Altfeld M. Polymorphisms in interferon regulatory factor 7 reduce interferon alpha responses of plasmacytoid dendritic cells to HIV-1. AIDS 2011;25(5):715–7

Chang JJ, Woods M, Lindsay RJ, Doyle EH, Griesbeck M, Chan ES, et al. Higher expression of several interferon-stimulated genes in HIV-1-infected females after adjusting for the level of viral replication. J Infect Dis 2013;208(5):830–8

Sterling TR, Vlahov D, Astemborski J, Hoover DR, Margolick JB, Quinn TC. Initial plasma HIV- 1 RNA levels and progression to AIDS in women and men. N Engl J Med 2001;344(10):720–5

Seddiki N, Brezar V, Draenert R. Cell exhaustion in HIV-1 infection: role of suppressor cells. Curr Opin HIV AIDS 2014;9:452-8.

Veazey RS, DeMaria M, Chalifoux LV, Shvetz DE, Pauley DR, Knight HL, et al. Gastrointestinal tract as a major site of CD4+ T cell depletion and viral repli- cation in SIV infection. Science 1998;280(5362):427–31

Brenchley JM, Schacker TW, Ruff LE, Price DA, Taylor JH, Beilman GJ, et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med 2004;200:749–59

Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 2006;12:1365–71

Gordon SN, Cervasi B, Odorizzi P, Silverman R, Aberra F, Ginsberg G, et al. Disruption of intestinal CD4+ T cell homeostasis is a key marker of systemic CD4+ T cell activation in HIV- infected individuals. J Immunol 2010;185:5169–79

Wallet MA, Rodriguez CA, Yin L, Saporta S, Chinratanapisit S, Hou W, et al. Microbial translocation induces persistent macrophage activation unrelated to HIV-1 levels or T-cell activation following therapy. AIDS 2010;24:1281–90

Brenchley JM, Price DA, Douek DC. HIV disease: fall out from a mucosal catastrophe? Nat Immunol 2006;7:235–9

Marchetti G, Bellistri GM, Borghi E, Tincati C, Ferramosca S, La FM, et al. Microbial translocation is associated with sustained failure in CD4+ T-cell reconstitution in HIV-infected patients on long term highly active antiretroviral therapy. AIDS 2008;22:2035–8

Kalayjian RC, Machekano RN, Rizk N, Robbins GK, Gandhi RT, Rodriguez BA, et al. Pretreatment levels of soluble cellular receptors and interleukin 6 are associated with HIV disease progression in subjects treated with highly active antiretroviral therapy. J Infect Dis 2010;201:1796–805

Casso lE, Malfeld S, Mahasha P, van der Merwe MS, Casso lS, Seebregts C, etal. Persistent microbial translocation and immune activation in HIV-1infected South Africans receiving combination antiretroviral therapy. J Infect Dis 2010;202:723–33

Brenchley JM, Paiardini M, Knox KS, Asher AI, Cervasi B, Asher TE, et al. Differential Th17 CD4T-cell depletion in pathogenic and non- pathogenic lentiviral infections. Blood 2008;112:2826–35

Littman DR, Rudensky AY. Th17 and regulatory T cells inmediating and restraining inflammation. Cell 2010;140:845–58

Pallikkuth S, Micci L, Ende ZS, Iriele RI, Cervasi B, Lawson B, et al. Maintenance of intestinal Th17 cells and reduced microbial translocation in SIV- infected rhesus macaques treated with interleukin (IL)-21. PLoS Pathog 2013;9(e1003471

Favre D, Lederer S, Kanwar B, Ma ZM, Proll S, Kasakow Z, et al. Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection. PLoS Pathog 2009;5:e1000295

Roederer M, Gregson Dubs J, Anderson MT, Raju PA, Herzenberg LA, Herzenberg L. CD8 naive T cell counts decrease progressively in HIV-infected adults. J Clin Invest 1995;95:2061–6

Ribeiro RM, Mohri H, Ho DD, Perelson AS. In vivo dynamics of T cell activation, proliferation, and death in HIV-1 infection: why are CD4+ but not CD8+ T cells depleted? Proc Natl Acad Sci US A 2002;99:15572–7

Zeng M, Smith AJ, Wietgrefe SW, Southern PJ, Schacker TW, Reilly CS, et al.

Cumulative mechanisms of lymphoid tissue fibrosis and T cell depletion in HIV-

and SIV infections. J Clin Invest 2011;121:998–1008

Clark DR, Repping S, Pakker NG, Prins JM, Notermans DW, Wit FW, et al. T-cell progenitor function during progressive human immunodeficiency virus-1 infection and after antiretroviral therapy. Blood 2000;96:242–9

Day CL, Kaufmann DE, Kiepiela P, Brown JA, Moodley ES, Reddy S, et al. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 2006;443:350–4

Trautmann L, Janbazian L, Chomont N, Said EA, Gimmig S, Bessette B, et al. Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat Med 2006;12:1198–202

Kaufmann DE, Kavanagh DG, Pereyra F, Zaunders JJ, Mackey EW, Miura T, et al. Upregulation of CTLA-4 by HIV-specific CD4+ T cells correlates with disease progression and defines a reversible immunedysfunction. Nat Immunol 2007;8:1246–54

Zhang Z, Xu X, Lu J, Zhang S, Gu L, Fu J, et al. B and T lymphocyte attenuator downregulation by HIV-1 depend son type I interferon and contributes to T-cell hyperactivation. J Infect Dis 2011;203:1668–78

Champagne P, Ogg GS, King AS, Knabenhans C, Ellefsen K, Nobile M, etal. Skewed maturation of memory HIV-specific CD8 T lymphocytes. Nature 2001;410:106–11

Migueles SA, Laborico AC, Shupert WL, Sabbaghian MS, Rabin R, Hallahan CW, etal. HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in non-progressors. Nat Immunol 2002;3:1061–8

Younes SA, Yassine-Diab B, Dumont AR, Boulasse lMR, Grossman Z, Routy JP, et al. HIV-1 viremia prevents the establishment of interleukin 2- producing HIV-specific memory CD4+ T cells endowed with proliferative capacity. J Exp Med 2003;198:1909–22

Harari A, Vallelian F, Meylan PR, Pantaleo G. Functional heterogeneity of memory CD4T cell responses indifferent conditions of antigen exposure and persistence. J Immunol 2005;174:1037–45

Schellens IM, Borghans JA, Jansen CA, De Cuyper IM, Geskus RB, van Baarle D, et al. Abundance of early functional HIV-specific CD8+ T cells does not predict AIDS-free survival time. PLoS One 2008;3:e2745

Pereyra F, Jia X, McLaren PJ, Telenti A, de Bakker PI, Walker BD, et al. The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 2010;330(6010):1551–7

Moir, S, Malaspina A, Ogwaro KW, et al. HIV-1 induces phenotypic and functional perturbations of B cells in chronically infected individuals. Proc. Natl Acad. Sci. USA 2001;98;10362–7

Boliar S, Murphy MK, Tran C, et al. B-Lymphocyte Dysfunction in Chronic HIV-1 Infection Does Not Prevent Cross-Clade Neutralization Breadth. J Virol 2012;86:8031-40

Moir S, Fauci AS. B cells in HIV infection and disease. Nat Rev Immunol 2009;9(4):235–45

Qiao X, He B, Chiu A, Knowles DM, et al. Human immunodeficiency virus 1 Nef suppresses CD40-dependent immunoglobulin class switching in bystander B cells. Nat Immunol 2006;7:302-10

Cubas RA, Mudd JC, Savoye AL, et al. Inadecuade T folicular cell help impairs

B cell immunity during HIV infection. Nat Med 2013;19:494-9

Moir S, Fauci AS. Pathogenic mechanisms of B-lymphocyte dysfunction in HIV disease. J Allergy Clin Immunol 2008;122:12-9

Cagigi A, Mowafi F, Phuong Dang LV, Tenner-Racz K, Atlas A, Grutzmeier

S, Racz P, Chiodi F, Nilsson A. Altered expression of the receptor-ligand pair CXCR5/CXCL13 in B cells during chronic HIV-1 infection. Blood 2008; 112:4401-10

De Milito A, Nilsson A, Titanji K, Thorstensson R, Reizenstein E, Narita M, et al. Mechanisms of hypergammaglobulinemia and impaired antigen-specific humoral immunity in HIV-1 infection. Blood 2004;103:2180—6

Cagigi A, Nilsson A, De Milito A, Chiodi F. B cell immunopathology during HIV1 infection: lessons to learn for HIV-1 vaccine design. Vaccine 2008;26:3016–

Zheng Z, Xu X, Lv J, et al. B and T Lymphocyte Attenuator Down-regulation by HIV-1 Depends on Type I Interferon and Contributes to T-Cell Hyperactivation. J Infect Dis 2011;203:1668–78

Brunetta E, Hudspeth KL, Mavilio D. Pathologic natural killer cell subset redistribution in HIV-1 infection: new insights in pathophysiology and clinical outcomes. J Leukoc Biol 2010;88:1119-30

Tiemesen CT, Paximadis M, Minevich G, et al. Natural Killer Cell Responses to HIV-1 Peptides are Associated With More Activating KIR Genes and HLA-C Genes of the C1 Allotype. J Acquir Immune Defic Syndr 2011;57:181-9

Norris S, Coleman A, Kuri-Cervantes L, et al. PD-1 expression on Natural Killer Cells and CD8+ T Cells during chronic HIV-1 infection. Viral Immunol 2012;25;329-31

De Maria A, Fogli M, Costa P, et al. The impaired NK cell cytolytic function in viremic HIV-1 infection is associated with a reduced surface expression of natural cytotoxicity receptors (NKp46, NKp30 and NKp44). Eur J Immunol 2003;33;2410-8

Sowrirajan B, Barker E. The Natural Killer Cell Cytotoxic Function Is Modulated by HIV-1 Accessory Proteins. Viruses 2011;3(7):1091-111

Shah AH, Sowrirajan B, Davis ZB, Ward JP, Campbell EM, Planelles V, Barker E. Degranulation of natural killer cells following interaction with HIV-1infected cells is hindered by downmodulation of NTB-A by Vpu. Cell Host Microbe 2010;8:397-409

Funke J, Dürr R, Dietrich U, Koch J. Natural Killer Cells in HIV-1 Infection: A Double-Edged Sword. AIDS Rev 2011;13:67-76

Perferrini JL, Castedo M, Roumier T, Andreau K, Nardacci R, Piacentini M, Kroemer G. Mechanisms of apoptosis induction by the HIV-1 envelope. Cell Death Differ 2005;12(Suppl 1);916-23

Phillips AN, Neaton J, Lundgren JD. The role of HIV in serious diseases other than AIDS. AIDS 2008;22:2409–18

Tebas P, Henry WK, Matining R, Weng-Cherng D, Schmitz J, Valdez H, et al. Metabolic and immuneactivation effects of treatment interruption in chronic

HIV-1 infection: implications for cardiovascular risk. PLoS One 2008;3:e2021

Holmberg SD, Moorman AC, Williamson JM, Tong TC, Ward DJ, Wood KC, et al. Protease inhibitors and cardiovascular outcomes in patients with HIV-1. Lancet 2002;360:1747–8

Friis-Moller N, Reiss P, Sabin CA, Weber R, Monforte A, El-Sadr W, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007;356:1723–35

Bozzette SA, Ake CF, Tam HK, Chang SW, Louis TA. Cardiovascular and cerebrovascular events in patients treated for human immunodeficiency virus infection. N Engl J Med 2003;348:702–10

Hsue PY, Hunt PW, Schnell A, Kalapus SC, Hoh R, Ganz P, et al. Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV-associated atherosclerosis. AIDS 2009;23:1059–67

Deeks SG, Gandhi RT, Chae CU, Lewandrowski KB. Case 30-2012: A 54-YearOld Woman with HIV Infection, Dyspnea, and Chest Pain. N Engl J Med

;367:1246-54

Barouch DH. The Quest for an HIV-1 Vaccine – Moving Foward. N Eng J Med 2013;369;2073-76

Norton TD, Miller EA. Recent Advances in Lentiviral Vaccines for HIV-1 Infection. Front Immunol 2016;7:1–8.

Hammer SM, Sobiesczyk ME, Janes H, Karuna ST, Mulligan MJ, Grove D et al. Efficacy Trial of a DNA/rAd5 HIV-1 preventive vaccine. N Eng J Med 2013;369;2083-92

Levy Y, Gahery-Segard H, Durier C, Lascaux AS, Goujard C, Meiffredy V et al. Immunological and virological efficacy of a therapeutic immunization combined with interleukin-2 in chronically HIV-1 infected patients. AIDS 2005;19:279–86

Levy Y, Durier C, Lascaux AS, Meiffrédy V, Gahéry-Ségard H, Goujard C et al. Sustained control of viremia following therapeutic immunization in chronically HIV-1 infected individuals. AIDS 2006;20;405–13

Autran B, Murphy RL, Costagliola D, Tubiana R, Clotet B, Gatell J et al. Greater viral rebound and reduced time to resume antiretroviral therapy after therapeutic immunization with the ALVAC-HIV vaccine (vCP1452). AIDS 2008;22;1313-22

Virgin HW, Walker BD. Immunology and the elusive AIDS vaccine. Nature 2010;464:224–31

Burton DR, Weiss RA. AIDS/HIV. A boost for HIV vaccine design. Science 2010;329:770–3

Abrams D, Levy Y, Losso MH, Babiker A, Collins G, Cooper DA, et al. Interleukin-2 therapy in patients with HIV infection. N Engl J Med 2009;361:1548–59.

Sportes C, Hakim FT, Memon SA, Zhang H, Chua KS, Brown MR, et al. Administration of rhIL-7 in humans increases invivo TCR repertoire diversity

by preferential expansion of naive T cell subsets. J Exp Med 2008;205:1701–

Sereti I, Dunham RM, Spritzler J, Aga E, Proschan MA, Medvik K, et al. IL-7 administration drives Tcell cycle entry and expansion in HIV-1 infection. Blood 2009;113(25): 6304–14

Levy Y, Lacabaratz C, WeissL, Viard JP, Goujard C, Lelievre JD, et al. Enhanced T cell recovery in HIV-1-infected adults through IL-7 treatment. J Clin Invest 2009;119:997–1007

Napolitano LA, Schmidt D, Gotway MB, Ameli N, Filbert EL, Ng MM, et al. Growth hormone enhances thymic function in HIV-1 infected adults. J Clin Invest 2008;118:1085–98

Velu V, Titanji K, Zhu B, Husain S, Pladevega A, LaiL, et al. Enhancing SIVspecific immunity in vivo by PD-1 blockade. Nature 2009;458:206–10

Dyavar SR, Velu V, Titanji K, Bosinger SE, Freeman GJ, Silvestri G, et al PD-1 blockade during chronic SIV infection reduces hyperimmune activation and microbial translocation in rhesus macaques. J Clin Invest 2012;122:1712–6

Markowitz M, Vaida F, Hare CB, Boden D, Mohri H, Hecht FM, et al. The virologic and immunologic effects of cyclosporine as an adjunct to antiretroviral therapy in patients treated during acute and early HIV-1infection. J Infect Dis 2010;201:1298–302

Vrisekoop N, Sankatsing SU, Jansen CA, Roos MT, Otto SA, Schuitemaker H, et al. Short communication: no detrimental immunological effects of mycophenolate mofetil and HAART in treatment-naive acute and chronic HIV-

-infected patients. AIDS Res Hum Retroviruses 2005;21:991–6

Cepeda EJ, Williams FM, Ishimori ML, Weisman MH, Reveille JD. The use of anti-tumour necrosis factor therapy in HIV-positive individuals with rheumatic disease. Ann Rheum Dis 2008;67:710–2

Tabb B, Morcock DR, Trubey CM, Quinones OA, Hao XP, Smedley J, et al. Reduced inflammation and lymphoid tissue immunopathology in rhesus macaques receiving anti-tumor necrosis factor treatment during primary simian immunodeficiency virus infection. J Infect Dis 2013;207:880–92

Hennessy EJ, Parker AE, O’Neill LA. Targeting toll-like receptors: emerging therapeutics? Nat Rev Drug Discov 2010;9:293–307

Descargas

Publicado

2017-02-01 — Actualizado el 2017-02-02

Versiones

Cómo citar

Cheng, H. C. C., Rodríguez, S. L. M., & Mora, M. del R. E. (2017). Activación inmunológica crónica en la patogénesis de la enfermedad por virus de inmunodeficiencia humana. Acta Médica Costarricense, 59(1), 7–14. https://doi.org/10.51481/amc.v59i1.947 (Original work published 1 de febrero de 2017)