CD8(+) Lymphocytes Suppress Human Immunodeficiency Virus 1 Replication by Secreting Type I Interferons

Overview

Journal J Interferon Cytokine Res

Publisher Mary Ann Liebert

Specialty Allergy & Immunology

Date 2013 Feb 14

PMID 23402527

Citations 7

Authors

M Scott Killian

Fernando Teque

Robert L Walker

Paul S Meltzer

J Keith Killian

Affiliations

Soon will be listed here.

Abstract

CD8(+) cells can suppress human immunodeficiency virus 1 (HIV-1) replication by releasing soluble factors. In 26 years of intensive research efforts, the identity of the major CD8(+) cell antiviral factor has remained elusive. To investigate the mechanism for this antiviral immune response, we performed gene expression analyses on primary CD4(+) cells that were exposed to HIV-suppressing CD8(+) cells or CD8(+) cell-conditioned medium having HIV-suppressing activity. These experiments revealed increased levels of multiple genes stimulated by type I interferons (IFN; eg, IFN-α and IFN-β). Further evaluation revealed that primary CD8(+) cells, particularly those from elite controllers and other asymptomatic HIV-1-infected individuals, secrete IFN, and this response directly contributes to the in vitro suppression of HIV replication in CD4(+) cells. This novel immune response, likely mediated by memory CD8(+) T cells, may play an important role in a wide variety of viral infections, cancers, and autoimmune diseases.

Citing Articles

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References

Tanabe Y, Nishibori T, Su L, Arduini R, Baker D, David M . Cutting edge: role of STAT1, STAT3, and STAT5 in IFN-alpha beta responses in T lymphocytes. J Immunol. 2005; 174(2):609-13. DOI: 10.4049/jimmunol.174.2.609. View

Sperber S, Hunger S, Schwartz B, Pestka S . Anti-rhinoviral activity of recombinant and hybrid species of interferon alpha. Antiviral Res. 1993; 22(2-3):121-9. DOI: 10.1016/0166-3542(93)90090-6. View

Killian M, Johnson C, Teque F, Fujimura S, Levy J . Natural suppression of human immunodeficiency virus type 1 replication is mediated by transitional memory CD8+ T cells. J Virol. 2010; 85(4):1696-705. PMC: 3028886. DOI: 10.1128/JVI.01120-10. View

Sauce D, Larsen M, Fastenackels S, Pauchard M, Ait-Mohand H, Schneider L . HIV disease progression despite suppression of viral replication is associated with exhaustion of lymphopoiesis. Blood. 2011; 117(19):5142-51. PMC: 3109539. DOI: 10.1182/blood-2011-01-331306. View

Payvandi F, Amrute S, Fitzgerald-Bocarsly P . Exogenous and endogenous IL-10 regulate IFN-alpha production by peripheral blood mononuclear cells in response to viral stimulation. J Immunol. 1998; 160(12):5861-8. View

Mackewicz C, Wang B, Metkar S, Richey M, Froelich C, Levy J . Lack of the CD8+ cell anti-HIV factor in CD8+ cell granules. Blood. 2003; 102(1):180-3. DOI: 10.1182/blood-2002-10-3034. View

Hoffman A, Banapour B, Levy J . Characterization of the AIDS-associated retrovirus reverse transcriptase and optimal conditions for its detection in virions. Virology. 1985; 147(2):326-35. DOI: 10.1016/0042-6822(85)90135-7. View

Maitra R, Silverman R . Regulation of human immunodeficiency virus replication by 2',5'-oligoadenylate-dependent RNase L. J Virol. 1998; 72(2):1146-52. PMC: 124589. DOI: 10.1128/JVI.72.2.1146-1152.1998. View

Castelli J, Deeks S, Shiboski S, Levy J . Relationship of CD8(+) T cell noncytotoxic anti-HIV response to CD4(+) T cell number in untreated asymptomatic HIV-infected individuals. Blood. 2002; 99(11):4225-7. DOI: 10.1182/blood-2001-11-0078. View

10.

Mackewicz C, Ortega H, Levy J . CD8+ cell anti-HIV activity correlates with the clinical state of the infected individual. J Clin Invest. 1991; 87(4):1462-6. PMC: 295198. DOI: 10.1172/JCI115153. View

11.

Killian M, Roop J, Ng S, Hecht F, Levy J . CD8+ cell anti-HIV activity rapidly increases upon discontinuation of early antiretroviral therapy. J Clin Immunol. 2009; 29(3):311-8. DOI: 10.1007/s10875-009-9275-y. View

12.

Brandt E, Linnane A, Devenish R . Expression of IFN A genes in subpopulations of peripheral blood cells. Br J Haematol. 1994; 86(4):717-25. DOI: 10.1111/j.1365-2141.1994.tb04820.x. View

13.

Rempel H, Sun B, Calosing C, Pillai S, Pulliam L . Interferon-alpha drives monocyte gene expression in chronic unsuppressed HIV-1 infection. AIDS. 2010; 24(10):1415-23. PMC: 2991092. DOI: 10.1097/QAD.0b013e32833ac623. View

14.

Moll H, Maier T, Zommer A, Lavoie T, Brostjan C . The differential activity of interferon-α subtypes is consistent among distinct target genes and cell types. Cytokine. 2010; 53(1):52-9. PMC: 3020287. DOI: 10.1016/j.cyto.2010.09.006. View

15.

Zhang L, Yu W, He T, Yu J, Caffrey R, Dalmasso E . Contribution of human alpha-defensin 1, 2, and 3 to the anti-HIV-1 activity of CD8 antiviral factor. Science. 2002; 298(5595):995-1000. DOI: 10.1126/science.1076185. View

16.

Mackewicz C, Craik C, Levy J . The CD8+ cell noncytotoxic anti-HIV response can be blocked by protease inhibitors. Proc Natl Acad Sci U S A. 2003; 100(6):3433-8. PMC: 152310. DOI: 10.1073/pnas.0630379100. View

17.

Golgher R, Paucker K . Immunology of interferons. II. Heterospecific activities of human interferons and their neutralization by antibody. J Immunol. 1970; 104(4):791-7. View

18.

Matikainen S, Sareneva T, Ronni T, Lehtonen A, Koskinen P, Julkunen I . Interferon-alpha activates multiple STAT proteins and upregulates proliferation-associated IL-2Ralpha, c-myc, and pim-1 genes in human T cells. Blood. 1999; 93(6):1980-91. View

19.

Davenport M, Petravic J . CD8+ T cell control of HIV--a known unknown. PLoS Pathog. 2010; 6(1):e1000728. PMC: 2813270. DOI: 10.1371/journal.ppat.1000728. View

20.

Kaimal V, Bardes E, Tabar S, Jegga A, Aronow B . ToppCluster: a multiple gene list feature analyzer for comparative enrichment clustering and network-based dissection of biological systems. Nucleic Acids Res. 2010; 38(Web Server issue):W96-102. PMC: 2896202. DOI: 10.1093/nar/gkq418. View