Altered T-Cell Subsets are Associated with Dysregulated Cytokine Secretion of CD4⁺ T Cells During HIV Infection

References

• Saharia KK, Koup RA. T cell susceptibility to HIV influences outcome of opportunistic infections. Cell. 2013;155(3):505–514. doi:10.1016/j.cell.2013.09.045
   PubMed Web of Science ®Google Scholar
• Laidlaw BJ, Craft JE, Kaech SM. The multifaceted role of CD4(+) T cells in CD8(+) T cell memory. Nat Rev Immunol. 2016;16(2):102–111. doi:10.1038/nri.2015.10
   PubMed Web of Science ®Google Scholar
• Boucau J, Madouasse J, Kourjian G, et al. The activation state of CD4 T cells alters cellular Peptidase activities, HIV antigen processing, and MHC class I presentation in a sequence-dependent manner. J Immunol. 2019;202(10):2856–2872. doi:10.4049/jimmunol.1700950
   PubMed Web of Science ®Google Scholar
• Porichis F, Hart MG, Massa A, et al. Immune checkpoint blockade restores HIV-specific CD4 T cell help for NK cells. J Immunol. 2018;201(3):971–981. doi:10.4049/jimmunol.1701551
   PubMed Web of Science ®Google Scholar
• Catalfamo M, Le Saout C, Lane HC. The role of cytokines in the pathogenesis and treatment of HIV infection. Cytokine Growth Factor Rev. 2012;23(4–5):207–214. doi:10.1016/j.cytogfr.2012.05.007
   PubMed Web of Science ®Google Scholar
• Klein SA, Dobmeyer JM, Dobmeyer TS, et al. Demonstration of the Th1 to Th2 cytokine shift during the course of HIV-1 infection using cytoplasmic cytokine detection on single cell level by flow cytometry. AIDS. 1997;11(9):1111–1118. doi:10.1097/00002030-199709000-00005
   PubMed Web of Science ®Google Scholar
• Romagnani S. Biology of human TH1 and TH2 cells. J Clin Immunol. 1995;15(3):121–129. doi:10.1007/BF01543103
   PubMed Web of Science ®Google Scholar
• Altfeld M, Addo MM, Kreuzer KA, et al. T(H)1 to T(H)2 shift of cytokines in peripheral blood of HIV-infected patients is detectable by reverse transcriptase polymerase chain reaction but not by enzyme-linked immunosorbent assay under nonstimulated conditions. J Acquir Immune Defic Syndr. 2000;23(4):287–294. doi:10.1097/00126334-200004010-00001
   PubMed Web of Science ®Google Scholar
• Sindhu S, Toma E, Cordeiro P, Ahmad R, Morisset R, Menezes J. Relationship of in vivo and ex vivo levels of TH1 and TH2 cytokines with viremia in HAART patients with and without opportunistic infections. J Med Virol. 2006;78(4):431–439. doi:10.1002/jmv.20558
   PubMed Web of Science ®Google Scholar
• Bahbouhi B, Landay A, Al-Harthi L. Dynamics of cytokine expression in HIV productively infected primary CD4+ T cells. Blood. 2004;103(12):4581–4587. doi:10.1182/blood-2003-12-4172
   PubMed Web of Science ®Google Scholar
• Santinelli L, Statzu M, Pierangeli A, et al. Increased expression of IL-32 correlates with IFN-γ, Th1 and Tc1 in virologically suppressed HIV-1-infected patients. Cytokine. 2019;120:273–281. doi:10.1016/j.cyto.2019.01.012
   PubMed Web of Science ®Google Scholar
• Reuter MA, Pombo C, Betts MR. Cytokine production and dysregulation in HIV pathogenesis: lessons for development of therapeutics and vaccines. Cytokine Growth Factor Rev. 2012;23(4–5):181–191. doi:10.1016/j.cytogfr.2012.05.005
   PubMed Web of Science ®Google Scholar
• Végran F, Berger H, Boidot R, et al. The transcription factor IRF1 dictates the IL-21-dependent anticancer functions of TH9 cells. Nat Immunol. 2014;15(8):758–766. doi:10.1038/ni.2925
   PubMed Web of Science ®Google Scholar
• Klatt NR, Estes JD, Sun X, et al. Loss of mucosal CD103+ DCs and IL-17+ and IL-22+ lymphocytes is associated with mucosal damage in SIV infection. Mucosal Immunol. 2012;5(6):646–657. doi:10.1038/mi.2012.38
   PubMed Web of Science ®Google Scholar
• Fakruddin JM, Lempicki RA, Gorelick RJ, et al. Noninfectious papilloma virus-like particles inhibit HIV-1 replication: implications for immune control of HIV-1 infection by IL-27. Blood. 2007;109(5):1841–1849. doi:10.1182/blood-2006-02-001578
   PubMed Web of Science ®Google Scholar
• Brenchley JM, Paiardini M, Knox KS, et al. Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood. 2008;112(7):2826–2835. doi:10.1182/blood-2008-05-159301
   PubMed Web of Science ®Google Scholar
• Micci L, Cervasi B, Ende ZS, et al. Paucity of IL-21-producing CD4(+) T cells is associated with Th17 cell depletion in SIV infection of rhesus macaques. Blood. 2012;120(19):3925–3935. doi:10.1182/blood-2012-04-420240
   PubMed Web of Science ®Google Scholar
• Gorenec L, Zidovec Lepej S, Grgic I, et al. The comparison of Th1, Th2, Th9, Th17 and Th22 cytokine profiles in acute and chronic HIV-1 infection. Microb Pathog. 2016;97:125–130. doi:10.1016/j.micpath.2016.06.008
   PubMed Web of Science ®Google Scholar
• Imamichi T, Yang J, Huang DW, et al. IL-27, a novel anti-HIV cytokine, activates multiple interferon-inducible genes in macrophages. AIDS. 2008;22(1):39–45. doi:10.1097/QAD.0b013e3282f3356c
   PubMed Web of Science ®Google Scholar
• Dai L, Lidie KB, Chen Q, et al. IL-27 inhibits HIV-1 infection in human macrophages by down-regulating host factor SPTBN1 during monocyte to macrophage differentiation. J Exp Med. 2013;210(3):517–534. doi:10.1084/jem.20120572
   PubMed Web of Science ®Google Scholar
• Ciuffreda D, Comte D, Cavassini M, et al. Polyfunctional HCV-specific T-cell responses are associated with effective control of HCV replication. Eur J Immunol. 2008;38(10):2665–2677. doi:10.1002/eji.200838336
   PubMed Web of Science ®Google Scholar
• Qiu Z, Zhang M, Zhu Y, et al. Multifunctional CD4 T cell responses in patients with active tuberculosis. Sci Rep. 2012;2(1):216. doi:10.1038/srep00216
   PubMedGoogle Scholar
• Casazza JP, Betts MR, Price DA, et al. Acquisition of direct antiviral effector functions by CMV-specific CD4+ T lymphocytes with cellular maturation. J Exp Med. 2006;203(13):2865–2877. doi:10.1084/jem.20052246
   PubMed Web of Science ®Google Scholar
• Duvall MG, Precopio ML, Ambrozak DA, et al. Polyfunctional T cell responses are a hallmark of HIV-2 infection. Eur J Immunol. 2008;38(2):350–363. doi:10.1002/eji.200737768
   PubMed Web of Science ®Google Scholar
• Lacy P, Stow JL. Cytokine release from innate immune cells: association with diverse membrane trafficking pathways. Blood. 2011;118(1):9–18. doi:10.1182/blood-2010-08-265892
   PubMed Web of Science ®Google Scholar
• Geginat J, Paroni M, Facciotti F, et al. The CD4-centered universe of human T cell subsets. Semin Immunol. 2013;25(4):252–262. doi:10.1016/j.smim.2013.10.012
   PubMed Web of Science ®Google Scholar
• Akase IE, Musa B, Obiako RO, Ahmad Elfulatiy A, Mohammed AA. Immune dysfunction in HIV: a possible role for pro- and anti-inflammatory cytokines in HIV staging. J Immunol Res. 2017;2017:4128398. doi:10.1155/2017/4128398
   PubMed Web of Science ®Google Scholar
• Godfried MH, van der Poll T, Weverling GJ, et al. Soluble receptors for tumor necrosis factor as predictors of progression to AIDS in asymptomatic human immunodeficiency virus type 1 infection. J Infect Dis. 1994;169(4):739–745. doi:10.1093/infdis/169.4.739
   PubMed Web of Science ®Google Scholar
• Lederman MM, Funderburg NT, Sekaly RP, Klatt NR, Hunt PW. Residual immune dysregulation syndrome in treated HIV infection. Adv Immunol. 2013;119:51–83. doi:10.1016/B978-0-12-407707-2.00002-3
   PubMed Web of Science ®Google Scholar
• Tincati C, Merlini E, Braidotti P, et al. Impaired gut junctional complexes feature late-treated individuals with suboptimal CD4+ T-cell recovery upon virologically suppressive combination antiretroviral therapy. AIDS. 2016;30(7):991–1003. doi:10.1097/QAD.0000000000001015
   PubMed Web of Science ®Google Scholar
• Younes SA, Talla A, Pereira Ribeiro S, et al. Cycling CD4+ T cells in HIV-infected immune nonresponders have mitochondrial dysfunction. J Clin Invest. 2018;128(11):5083–5094. doi:10.1172/JCI120245
   PubMed Web of Science ®Google Scholar
• Ipp H, Zemlin AE, Erasmus RT, Glashoff RH. Role of inflammation in HIV-1 disease progression and prognosis. Crit Rev Clin Lab Sci. 2014;51(2):98–111. doi:10.3109/10408363.2013.865702
   PubMed Web of Science ®Google Scholar
• Appay V, Sauce D. Immune activation and inflammation in HIV-1 infection: causes and consequences. J Pathol. 2008;214(2):231–241. doi:10.1002/path.2276
   PubMed Web of Science ®Google Scholar
• Boasso A, Shearer GM. Chronic innate immune activation as a cause of HIV-1 immunopathogenesis. Clin Immunol. 2008;126(3):235–242. doi:10.1016/j.clim.2007.08.015
   PubMed Web of Science ®Google Scholar
• Klatt NR, Chomont N, Douek DC, Deeks SG. Immune activation and HIV persistence: implications for curative approaches to HIV infection. Immunol Rev. 2013;254(1):326–342. doi:10.1111/imr.12065
   PubMedGoogle Scholar
• Kostense S, Vandenberghe K, Joling J, et al. Persistent numbers of tetramer+ CD8(+) T cells, but loss of interferon-gamma+ HIV-specific T cells during progression to AIDS. Blood. 2002;99(7):2505–2511. doi:10.1182/blood.v99.7.2505
   PubMed Web of Science ®Google Scholar
• Lieberman J, Manjunath N, Shankar P. Avoiding the kiss of death: how HIV and other chronic viruses survive. Curr Opin Immunol. 2002;14(4):478–486. doi:10.1016/s0952-7915(02)00366-7
   PubMed Web of Science ®Google Scholar
• Sakaguchi S. Control of immune responses by naturally arising CD4+ regulatory T cells that express toll-like receptors. J Exp Med. 2003;197(4):397–401. doi:10.1084/jem.20030012
   PubMed Web of Science ®Google Scholar
• 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(7):4407–4414. doi:10.4049/jimmunol.174.7.4407
   PubMed Web of Science ®Google Scholar
• Guarda G, Dostert C, Staehli F, et al. T cells dampen innate immune responses through inhibition of NLRP1 and NLRP3 inflammasomes. Nature. 2009;460(7252):269–273. doi:10.1038/nature08100
   PubMed Web of Science ®Google Scholar
• Kim KD, Zhao J, Auh S, et al. Adaptive immune cells temper initial innate responses. Nat Med. 2007;13(10):1248–1252. doi:10.1038/nm1633
   PubMed Web of Science ®Google Scholar
• Nakagawa F, May M, Phillips A. Life expectancy living with HIV: recent estimates and future implications. Curr Opin Infect Dis. 2013;26(1):17–25. doi:10.1097/QCO.0b013e32835ba6b1
   PubMed Web of Science ®Google Scholar
• May M, Gompels M, Delpech V, et al. Impact of late diagnosis and treatment on life expectancy in people with HIV-1: UK Collaborative HIV Cohort (UK CHIC) Study. BMJ. 2011;343:d6016. doi:10.1136/bmj.d6016
   PubMed Web of Science ®Google Scholar
• Amu S, Lantto Graham R, Bekele Y, et al. Dysfunctional phenotypes of CD4+ and CD8+ T cells are comparable in patients initiating ART during early or chronic HIV-1 infection. Medicine. 2016;95(23):e3738. doi:10.1097/MD.0000000000003738
   PubMed Web of Science ®Google Scholar
• Morou A, Brunet-Ratnasingham E, Dubé M, et al. Altered differentiation is central to HIV-specific CD4+ T cell dysfunction in progressive disease. Nat Immunol. 2019;20(8):1059–1070. doi:10.1038/s41590-019-0418-x
   PubMed Web of Science ®Google Scholar
• Kong Y, Tian Y, Hao Y, et al. Two types of poor immunological responder showing distinct responses to long-term HAART. Int J Infect Dis. 2019;86:178–187. doi:10.1016/j.ijid.2019.07.037
   PubMed Web of Science ®Google Scholar
• Khaitan A, Unutmaz D. Revisiting immune exhaustion during HIV infection. Curr HIV/AIDS Rep. 2011;8(1):4–11. doi:10.1007/s11904-010-0066-0
   PubMedGoogle Scholar
• Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol. 2015;15(8):486–499. doi:10.1038/nri3862
   PubMed Web of Science ®Google Scholar
• Crawford A, Angelosanto JM, Kao C, et al. Molecular and transcriptional basis of CD4+ T cell dysfunction during chronic infection. Immunity. 2014;40(2):289–302. doi:10.1016/j.immuni.2014.01.005
   PubMed Web of Science ®Google Scholar
• Wherry EJ. T cell exhaustion. Nat Immunol. 2011;12(6):492–499. doi:10.1038/ni.2035
   PubMed Web of Science ®Google Scholar
• Goding SR, Wilson KA, Xie Y, et al. Restoring immune function of tumor-specific CD4+ T cells during recurrence of melanoma. J Immunol. 2013;190(9):4899–4909. doi:10.4049/jimmunol.1300271
   PubMed Web of Science ®Google Scholar
• Dong Y, Li X, Zhang L, et al. CD4+ T cell exhaustion revealed by high PD-1 and LAG-3 expression and the loss of helper T cell function in chronic hepatitis B. BMC Immunol. 2019;20(1):27. doi:10.1186/s12865-019-0309-9
   PubMed Web of Science ®Google Scholar
• Kassu A, Marcus RA, D’Souza MB, et al. Regulation of virus-specific CD4+ T cell function by multiple costimulatory receptors during chronic HIV infection. J Immunol. 2010;185(5):3007–3018. doi:10.4049/jimmunol.1000156
   PubMed Web of Science ®Google Scholar
• Younes SA, Yassine-Diab B, Dumont AR, 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(12):1909–1922. doi:10.1084/jem.20031598
   PubMed Web of Science ®Google Scholar
• D’Souza M, Fontenot AP, Mack DG, et al. Programmed death 1 expression on HIV-specific CD4+ T cells is driven by viral replication and associated with T cell dysfunction. J Immunol. 2007;179(3):1979–1987. doi:10.4049/jimmunol.179.3.1979
   PubMed Web of Science ®Google Scholar
• Kaufmann DE, Kavanagh DG, Pereyra F, et al. Upregulation of CTLA-4 by HIV-specific CD4+ T cells correlates with disease progression and defines a reversible immune dysfunction. Nat Immunol. 2007;8(11):1246–1254. doi:10.1038/ni1515
   PubMed Web of Science ®Google Scholar
• Griesbeck M, Scully E, Altfeld M. Sex and gender differences in HIV-1 infection. Clin Sci. 2016;130(16):1435–1451. doi:10.1042/CS20160112
   Web of Science ®Google Scholar