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Erschienen in: Medical Microbiology and Immunology 3/2017

04.04.2017 | Original Investigation

Role of IL-21 in HTLV-1 infections with emphasis on HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)

verfasst von: Taraneh Rajaei, Hamid Farajifard, Houshang Rafatpanah, Reza Bustani, Narges Valizadeh, Bahareh Rajaei, Seyed Abdolrahim Rezaee

Erschienen in: Medical Microbiology and Immunology | Ausgabe 3/2017

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Abstract

Interleukin-21 (IL-21) enhances the survival and cytotoxic properties of cytotoxic T cells (CTLs) and exhibits essential roles in controlling chronic viral infections. HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive inflammatory disease of the nervous system. The main determinant of disease progression is efficiency of the CTL response to Human T lymphotropic virus types I (HTLV-1). In this study, the expression of host IL-21 and HTLV-I Tax and proviral load (PVL) was evaluated to understand the role and mechanism of IL-21 in HTLV-1 infections and the subsequent development of HAM/TSP. A cross-sectional study was carried out on 20 HAM/TSP patients, 20 asymptomatic HTLV-1 carriers (ACs) and 20 healthy controls (HCs) to evaluate the expression of IL-21 and Tax and PVL in non-activated and phorbol myristate acetate (PMA)-ionomycin-activated peripheral blood mononuclear cells (PBMCs). The mean mRNA expression of IL-21 in the non-activated and activated PBMCs was higher (by 5–13 times) in the HAM/TSP patients than in ACs and HCs (p < 0.05); however, there was no significant difference between ACs and HCs. In contrast to the IL-21 mRNA expression, the serum level of the IL-21 protein was significantly lower in the HAM/TSP patients than in ACs and HCs (p < 0.05). Furthermore, higher expression of Tax and PVL was observed in the HAM/TSP subjects than ACs (p < 0.05). In addition, Tax gene expression was positively correlated with PVL (R = 0.595, p = 0.000) and IL-21 gene expression (R = 0.395, p = 0.021) in the HTLV-1-infected subjects. In conclusion, the increase in IL-21 mRNA expression may reflect the attempt of infected T cells to induce an appropriate antiviral response, and the decrease in IL-21 protein expression may reflect the inhibition of IL-21 mRNA translation by viral factors in favour of virus evasion and dissemination.
Literatur
3.
Zurück zum Zitat Boostani R, Vakili R, Hosseiny SS et al (2015) Triple therapy with prednisolone, pegylated interferon and sodium valproate improves clinical outcome and reduces human T-cell leukemia virus type 1 (HTLV-1) proviral load, tax and HBZ mRNA expression in patients with HTLV-1-associated myelopathy/tropical. Neurother 12:887–895. doi:10.1007/s13311-015-0369-3 CrossRef Boostani R, Vakili R, Hosseiny SS et al (2015) Triple therapy with prednisolone, pegylated interferon and sodium valproate improves clinical outcome and reduces human T-cell leukemia virus type 1 (HTLV-1) proviral load, tax and HBZ mRNA expression in patients with HTLV-1-associated myelopathy/tropical. Neurother 12:887–895. doi:10.​1007/​s13311-015-0369-3 CrossRef
4.
Zurück zum Zitat Yari A, Rezaee SA, Valizadeh N et al (2014) Evaluation of HTLV-1 activity in HAM/TSP patients using proviral load and Tax mRNA expression after In Vitro lymphocyte activation. Iran J BasicMed Sci 17:531–536 Yari A, Rezaee SA, Valizadeh N et al (2014) Evaluation of HTLV-1 activity in HAM/TSP patients using proviral load and Tax mRNA expression after In Vitro lymphocyte activation. Iran J BasicMed Sci 17:531–536
7.
Zurück zum Zitat Massoud R, Enose-akahata Y, Tagaya Y, et al (2015) Common γ-chain blocking peptide reduces in vitro immune activation markers in HTLV-1-associated myelopathy/tropical spastic paraparesis. 112:2–7. doi:10.1073/pnas.1412626112 Massoud R, Enose-akahata Y, Tagaya Y, et al (2015) Common γ-chain blocking peptide reduces in vitro immune activation markers in HTLV-1-associated myelopathy/tropical spastic paraparesis. 112:2–7. doi:10.​1073/​pnas.​1412626112
9.
Zurück zum Zitat Tamayo O (2005) Autoimmunity and molecular mimicry in tropical spastic paraparesis/human myelopathy. 38:241–250 Tamayo O (2005) Autoimmunity and molecular mimicry in tropical spastic paraparesis/human myelopathy. 38:241–250
10.
16.
18.
Zurück zum Zitat Trautmann L, Janbazian L, Chomont N et al (2006) Upregulation of PD-1 expression on HIV-specific CD8 + T cells leads to reversible immune dysfunction. Nat Med 12:1198–1202. doi:10.1038/nm1482 CrossRefPubMed Trautmann L, Janbazian L, Chomont N et al (2006) Upregulation of PD-1 expression on HIV-specific CD8 + T cells leads to reversible immune dysfunction. Nat Med 12:1198–1202. doi:10.​1038/​nm1482 CrossRefPubMed
19.
Zurück zum Zitat Blackburn SD, Shin H, Haining WN et al (2009) Coregulation of CD8 + T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol 10:29–37. doi:10.1038/ni.1679 CrossRefPubMed Blackburn SD, Shin H, Haining WN et al (2009) Coregulation of CD8 + T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol 10:29–37. doi:10.​1038/​ni.​1679 CrossRefPubMed
22.
Zurück zum Zitat Chevalier MF, Julg B, Pyo A et al (2011) HIV-1-specific interleukin-21 + CD4 + T cell responses contribute to durable viral control through the modulation of HIV-specific CD8 + T cell function. J Virol 85:733–741. doi:10.1128/JVI.02030-10 CrossRefPubMed Chevalier MF, Julg B, Pyo A et al (2011) HIV-1-specific interleukin-21 + CD4 + T cell responses contribute to durable viral control through the modulation of HIV-specific CD8 + T cell function. J Virol 85:733–741. doi:10.​1128/​JVI.​02030-10 CrossRefPubMed
23.
Zurück zum Zitat Yue FY, Lo C, Sakhdari A et al (2010) HIV-specific IL-21 producing CD4 + T cells are induced in acute and chronic progressive HIV infection and are associated with relative viral control. J Immunol 185:498–506. doi:10.4049/jimmunol.0903915 CrossRefPubMed Yue FY, Lo C, Sakhdari A et al (2010) HIV-specific IL-21 producing CD4 + T cells are induced in acute and chronic progressive HIV infection and are associated with relative viral control. J Immunol 185:498–506. doi:10.​4049/​jimmunol.​0903915 CrossRefPubMed
24.
Zurück zum Zitat Iannello A, Boulassel MR, Samarani S et al (2010) IL-21 enhances NK cell functions and survival in healthy and HIV-infected patients with minimal stimulation of viral replication. J Leukoc Biol 87:857–867. doi:10.1189/jlb.1009701 CrossRefPubMed Iannello A, Boulassel MR, Samarani S et al (2010) IL-21 enhances NK cell functions and survival in healthy and HIV-infected patients with minimal stimulation of viral replication. J Leukoc Biol 87:857–867. doi:10.​1189/​jlb.​1009701 CrossRefPubMed
30.
Zurück zum Zitat Abdelbary NH, Abdullah HM, Matsuzaki T et al (2011) Reduced Tim-3 expression on human T-lymphotropic virus type I (HTLV-I) Tax-specific cytotoxic T lymphocytes in HTLV-I infection. J Infect Dis 203:948–959. doi:10.1093/infdis/jiq153 CrossRefPubMed Abdelbary NH, Abdullah HM, Matsuzaki T et al (2011) Reduced Tim-3 expression on human T-lymphotropic virus type I (HTLV-I) Tax-specific cytotoxic T lymphocytes in HTLV-I infection. J Infect Dis 203:948–959. doi:10.​1093/​infdis/​jiq153 CrossRefPubMed
31.
Zurück zum Zitat Everly DN Jr, Feng P, Mian IS, Read GS (2002) mRNA degradation by the virion host shutoff (Vhs) protein of herpes simplex virus: genetic and biochemical evidence that Vhs is a nuclease. J Virol 76:8560–8571CrossRefPubMed Everly DN Jr, Feng P, Mian IS, Read GS (2002) mRNA degradation by the virion host shutoff (Vhs) protein of herpes simplex virus: genetic and biochemical evidence that Vhs is a nuclease. J Virol 76:8560–8571CrossRefPubMed
32.
Zurück zum Zitat Matis J, Kudelova M (2001) Early shutoff of host protein synthesis in cells infected with herpes simplex viruses. Acta Virol 45:269–277PubMed Matis J, Kudelova M (2001) Early shutoff of host protein synthesis in cells infected with herpes simplex viruses. Acta Virol 45:269–277PubMed
33.
Zurück zum Zitat Matsuura E, Kubota R, Tanaka Y (2015) Visualization of HTLV-1 Y specific cytotoxic T lymphocytes in the spinal cords of patients with HTLV-1 Y associated myelopathy/tropical spastic paraparesis. 74:2–14 Matsuura E, Kubota R, Tanaka Y (2015) Visualization of HTLV-1 Y specific cytotoxic T lymphocytes in the spinal cords of patients with HTLV-1 Y associated myelopathy/tropical spastic paraparesis. 74:2–14
34.
Zurück zum Zitat Marcondes MC, Burudi EM, Huitron-Resendiz S et al (2001) Highly activated CD8(+) T cells in the brain correlate with early central nervous system dysfunction in simian immunodeficiency virus infection. J Immunol 167:5429–5438CrossRefPubMed Marcondes MC, Burudi EM, Huitron-Resendiz S et al (2001) Highly activated CD8(+) T cells in the brain correlate with early central nervous system dysfunction in simian immunodeficiency virus infection. J Immunol 167:5429–5438CrossRefPubMed
35.
Zurück zum Zitat Liu SM, Lee DH, Sullivan JM et al (2011) Differential IL-21 signaling in APCs leads to disparate Th17 differentiation in diabetes-susceptible NOD and diabetes-resistant NOD. Idd3 mice. J Clin Invest 121:4303–4310. doi:10.1172/JCI46187 CrossRefPubMedPubMedCentral Liu SM, Lee DH, Sullivan JM et al (2011) Differential IL-21 signaling in APCs leads to disparate Th17 differentiation in diabetes-susceptible NOD and diabetes-resistant NOD. Idd3 mice. J Clin Invest 121:4303–4310. doi:10.​1172/​JCI46187 CrossRefPubMedPubMedCentral
38.
39.
Zurück zum Zitat Monteleone G, Monteleone I, Fina D et al (2005) Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn’s disease. Gastroenterology 128:687–694CrossRefPubMed Monteleone G, Monteleone I, Fina D et al (2005) Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn’s disease. Gastroenterology 128:687–694CrossRefPubMed
42.
Zurück zum Zitat Herber D, Brown TP, Liang S et al (2007) IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R.Fc reduces disease progression. J Immunol 178:3822–3830CrossRefPubMed Herber D, Brown TP, Liang S et al (2007) IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R.Fc reduces disease progression. J Immunol 178:3822–3830CrossRefPubMed
43.
Zurück zum Zitat Young DA, Hegen M, Ma HL et al (2007) Blockade of the interleukin-21/interleukin-21 receptor pathway ameliorates disease in animal models of rheumatoid arthritis. Arthritis Rheum 56:1152–1163. doi:10.1002/art.22452 CrossRefPubMed Young DA, Hegen M, Ma HL et al (2007) Blockade of the interleukin-21/interleukin-21 receptor pathway ameliorates disease in animal models of rheumatoid arthritis. Arthritis Rheum 56:1152–1163. doi:10.​1002/​art.​22452 CrossRefPubMed
Metadaten
Titel
Role of IL-21 in HTLV-1 infections with emphasis on HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)
verfasst von
Taraneh Rajaei
Hamid Farajifard
Houshang Rafatpanah
Reza Bustani
Narges Valizadeh
Bahareh Rajaei
Seyed Abdolrahim Rezaee
Publikationsdatum
04.04.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Medical Microbiology and Immunology / Ausgabe 3/2017
Print ISSN: 0300-8584
Elektronische ISSN: 1432-1831
DOI
https://doi.org/10.1007/s00430-017-0492-3

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