Elevated expression of miR-155 is associated with the differentiation of CD8+ T cells in patients with HIV-1

Jin,Changzhong; Cheng,Linfang; Lu,Xiangyun; Xie,Tiansheng; Wu,Haibo; Wu,Nanping

doi:10.3892/mmr.2017.6755

Elevated expression of miR-155 is associated with the differentiation of CD8+ T cells in patients with HIV-1

Authors:
- Changzhong Jin
- Linfang Cheng
- Xiangyun Lu
- Tiansheng Xie
- Haibo Wu
- Nanping Wu
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Affiliations: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
Published online on: June 12, 2017 https://doi.org/10.3892/mmr.2017.6755
Pages: 1584-1589

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Abstract

The differentiation and response ofCD8+ T cells is vital in host defense against human immunodeficiency virus type 1 (HIV-1). MicroRNA (miR)‑155 is an important regulator of T cell differentiation. However, the profile of miR-155 in HIV‑1 infected individuals and its association with CD8+ T cell differentiation remain to be fully elucidated. The present cross‑sectional study was performed involving 63 HIV‑1‑infected patients undergoing highly active antiretroviral therapy (HAART), 31 HAART‑naïve patients and 35 healthy controls. The levels of miR‑155 in CD8+ T cells were detected using reverse transcription‑quantitative polymerase chain reaction analysis. Subsets of CD8+ T cell differentiation were detected using flow cytometry. The results revealed that the discord controllers and HAART‑naïve patients showed higher percentages of effector and effector memory cells, and lower percentages of naïve cells (P<0.05). The levels of miR‑155 in CD8+ T cells from the HIV‑1‑infected patients were higher, particularly in the discord controllers and HAART naïve patients (P<0.01). The expression levels of miR‑155 were positively correlated with the percentages of effector and effector memory CD8+ T cells, and negatively correlated with the percentages of naïve and central memory CD8+ T cells (P<0.01). Taken together, these findings suggested that the levels of miR‑155 in CD8+ T cells of patients with HIV-1 were increased and associated with CD8+ T cell differentiation.

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1	Morou A, Palmer BE and Kaufmann DE: Distinctive features of CD4⁺ T cell dysfunction in chronic viral infections. Curr Opin HIV AIDS. 9:446–451. 2014. View Article : Google Scholar : PubMed/NCBI
2	Jin CZ, Zhao Y, Zhang FJ, Yao HP, Wu LJ, Zhao HX, Wei HS and Wu NP: Different plasma levels of interleukins and chemokines: Comparison between children and adults with AIDS in China. Chin Med J (Engl). 122:530–535. 2009.PubMed/NCBI
3	Chitra Y, Urgen S, Dayananda I and Brajachand SN: Effect of anti retroviral therapy (ART) on CD4 T lymphocyte count and the spectrum of opportunistic infections in HIV/AIDS in Manipur. J Commun Dis. 41:19–24. 2009.PubMed/NCBI
4	Lu W, Mehraj V, Vyboh K, Cao W, Li T and Routy JP: CD4:CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV-positive patients. J Int AIDS Soc. 18:200522015. View Article : Google Scholar : PubMed/NCBI
5	Serrano-Villar S, Sainz T, Lee SA, Hunt PW, Sinclair E, Shacklett BL, Ferre AL, Hayes TL, Somsouk M, Hsue PY, et al: HIV-Infected Individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8⁺ T cell activation, and increased risk of non-AIDS morbidity and mortality. PLoS Pathog. 10:e10040782014. View Article : Google Scholar : PubMed/NCBI
6	Saeidi A, Buggert M, Che KF, Kong YY, Velu V, Larsson M and Shankar EM: Regulation of CD8⁺ T-cell cytotoxicity in HIV-1 infection. Cell Immunol. 298:126–133. 2015. View Article : Google Scholar : PubMed/NCBI
7	Mudd JC and Lederman MM: CD8 T cell persistence in treated HIV infection. Curr Opin HIV AIDS. 9:500–505. 2014. View Article : Google Scholar : PubMed/NCBI
8	Demers KR, Reuter MA and Betts MR: CD8(+) T-cell effector function and transcriptional regulation during HIV pathogenesis. Immunol Rev. 254:190–206. 2013. View Article : Google Scholar : PubMed/NCBI
9	Cao W, Mehraj V, Kaufmann DE, Li T and Routy JP: Elevation and persistence of CD8 T-cells in HIV infection: The Achilles heel in the ART era. J Int AIDS Soc. 19:206972016. View Article : Google Scholar : PubMed/NCBI
10	Allantaz F, Cheng DT, Bergauer T, Ravindran P, Rossier MF, Ebeling M, Badi L, Reis B, Bitter H, D'Asaro M, et al: Expression profiling of human immune cell subsets identifies miRNA-mRNA regulatory relationships correlated with cell type specific expression. PLoS One. 7:e299792012. View Article : Google Scholar : PubMed/NCBI
11	Ooi AG, Sahoo D, Adorno M, Wang Y, Weissman IL and Park CY: MicroRNA-125b expands hematopoietic stem cells and enriches for the lymphoid-balanced and lymphoid-biased subsets. Proc Natl Acad Sci USA. 107:21505–21510. 2010. View Article : Google Scholar : PubMed/NCBI
12	Zhang N and Bevan MJ: Dicer controls CD8⁺ T-cell activation, migration, and survival. Proc Natl Acad Sci USA. 107:21629–21634. 2010. View Article : Google Scholar : PubMed/NCBI
13	Salaun B, Yamamoto T, Badran B, Tsunetsugu-Yokota Y, Roux A, Baitsch L, Rouas R, Fayyad-Kazan H, Baumgaertner P, Devevre E, et al: Differentiation associated regulation of microRNA expression in vivo in human CD8⁺ T cell subsets. J Transl Med. 9:442011. View Article : Google Scholar : PubMed/NCBI
14	Tsai CY, Allie SR, Zhang W and Usherwood EJ: MicroRNA miR-155 affects antiviral effector and effector Memory CD8 T cell differentiation. J Virol. 87:2348–2351. 2013. View Article : Google Scholar : PubMed/NCBI
15	Singh UP, Murphy AE, Enos RT, Shamran HA, Singh NP, Guan H, Hegde VL, Fan D, Price RL, Taub DD, et al: miR-155 deficiency protects mice from experimental colitis by reducing T helper type 1/type 17 responses. Immunology. 143:478–489. 2014. View Article : Google Scholar : PubMed/NCBI
16	Yao R, Ma YL, Liang W, Li HH, Ma ZJ, Yu X and Liao YH: MicroRNA-155 modulates Treg and Th17 cells differentiation and Th17 cell function by targeting SOCS1. PLoS One. 7:e460822012. View Article : Google Scholar : PubMed/NCBI
17	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
18	Pender MP, Csurhes PA, Pfluger CM and Burrows SR: Deficiency of CD8⁺ effector memory T cells is an early and persistent feature of multiple sclerosis. Mult Scler. 20:1825–1832. 2014. View Article : Google Scholar : PubMed/NCBI
19	Groves KC, Bibby DF, Clark DA, Isaksen A, Deayton JR, Anderson J, Orkin C, Stagg AJ and McKnight A: Disease progression in HIV-1-infected viremic controllers. J Acquir Immune Defic Syndr. 61:407–416. 2012. View Article : Google Scholar : PubMed/NCBI
20	Mohan T, Bhatnagar S, Gupta DL and Rao DN: Current understanding of HIV-1 and T-cell adaptive immunity: Progress to date. Microb Pathog. 73:60–69. 2014. View Article : Google Scholar : PubMed/NCBI
21	Prlic M, Williams MA and Bevan MJ: Requirements for CD8 T-cell priming, memory generation and maintenance. Curr Opin Immunol. 19:315–319. 2007. View Article : Google Scholar : PubMed/NCBI
22	Joshi NS and Kaech SM: Effector CD8 T cell development: A balancing act between memory cell potential and terminal differentiation. J Immunol. 180:1309–1315. 2008. View Article : Google Scholar : PubMed/NCBI
23	Papagno L, Spina CA, Marchant A, Salio M, Rufer N, Little S, Dong T, Chesney G, Waters A, Easterbrook P, et al: Immune activation and CD8⁺ T-cell differentiation towards senescence in HIV-1 infection. PLoS Biol. 2:E202004. View Article : Google Scholar : PubMed/NCBI
24	Appay V, Papagno L, Spina CA, Hansasuta P, King A, Jones L, Ogg GS, Little S, McMichael AJ, Richman DD and Rowland-Jones SL: Dynamics of T cell responses in HIV infection. J Immunol. 168:3660–3666. 2002. View Article : Google Scholar : PubMed/NCBI
25	Seddiki N, Brezar V, Ruffin N, Lévy Y and Swaminathan S: Role of miR-155 in the regulation of lymphocyte immune function and disease. Immunology. 142:32–38. 2014. View Article : Google Scholar : PubMed/NCBI
26	Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, Pfeffer S, Rice A, Kamphorst AO, Landthaler M, et al: A mammalian microRNA expression atlas based on small RNA library sequencing. Cell. 129:1401–1414. 2007. View Article : Google Scholar : PubMed/NCBI
27	Escobar T, Yu CR, Muljo SA and Egwuagu CE: STAT3 activates miR-155 in Th17 cells and acts in concert to promote experimental autoimmune uveitis. Invest Ophthalmol Vis Sci. 54:4017–4025. 2013. View Article : Google Scholar : PubMed/NCBI
28	Thai TH, Calado DP, Casola S, Ansel KM, Xiao C, Xue Y, Murphy A, Frendewey D, Valenzuela D, Kutok JL, et al: Regulation of the germinal center response by microRNA-155. Science. 316:604–608. 2007. View Article : Google Scholar : PubMed/NCBI
29	Gracias DT, Stelekati E, Hope JL, Boesteanu AC, Doering TA, Norton J, Mueller YM, Fraietta JA, Wherry EJ, Turner M and Katsikis PD: The microRNA miR-155 controls CD8 (+) T cell responses by regulating interferon signaling. Nat Immunol. 14:593–602. 2013. View Article : Google Scholar : PubMed/NCBI
30	Lind EF, Elford AR and Ohashi PS: Micro-RNA 155 is required for optimal CD8⁺ T cell responses to acute viral and intracellular bacterial challenges. J Immunol. 190:1210–1216. 2013. View Article : Google Scholar : PubMed/NCBI
31	Bignami F, Pilotti E, Bertoncelli L, Ronzi P, Gulli M, Marmiroli N, Magnani G, Pinti M, Lopalco L, Mussini C, et al: Stable changes in CD4⁺ T lymphocyte miRNA expression after exposure to HIV-1. Blood. 119:6259–6267. 2012. View Article : Google Scholar : PubMed/NCBI
32	Seddiki N, Swaminathan S, Phetsouphanh C and Kelleher AD: miR-155 is differentially expressed in Treg subsets, which may explain expression level differences of miR-155 in HIV-1 infected patients. Blood. 119:6396–6397. 2012. View Article : Google Scholar : PubMed/NCBI
33	Martinez-Nunez RT, Louafi F, Friedmann PS and Sanchez-Elsner T: MicroRNA-155 modulates the pathogen binding ability of dendritic cells (DCs) by down-regulation of DC-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN). J Biol Chem. 284:16334–16342. 2009. View Article : Google Scholar : PubMed/NCBI