title: Ribavirin Does Not Impair the Suppressive Activity of Foxp3(+)CD4(+)CD25(+) Regulatory T Cells.
abstract: Ribavirin is an antiviral drug used in combination with pegylated interferon-α (IFN-α) for the treatment of hepatitis C virus (HCV) infection. Recently, ribavirin was reported to inhibit the suppressive activity of regulatory T (Treg) cells. In the present study, we re-evaluated the effect of ribavirin on Foxp3(+)CD4(+)CD25(+) Treg cells from normal donors. First, we examined the expression of CTLA-4 and CD39, which are known to play a role in the suppressive function of Treg cells. We found that ribavirin treatment did not modulate the expression of CTLA-4 and CD39 in Treg cells. We also studied the effect of ribavirin on Treg cells in the presence of IFN-α; however, the expression of CTLA-4 and CD39 in Treg cells was not changed by ribavirin in the presence of IFN-α. Next, we directly evaluated the effect of ribavirin on the suppressive activity of Treg cells in the standard Treg suppression assay, by co-culturing CFSE-labeled non-Treg CD4(+) T cells with purified Treg cells. We found that ribavirin did not attenuate the suppressive activity of Treg cells. Taken together, while ribavirin reversed Treg cell-mediated suppression of effector T cells in the previous study, we herein demonstrate that ribavirin does not impair the suppressive activity of Treg cells.
authors.affiliation: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, Korea.
authors.forename: Jeewon
authors.initials: J
authors.lastname: Lee
authors.forename: Yoon Seok
authors.initials: YS
authors.lastname: Choi
authors.forename: Eui-Cheol
authors.initials: EC
authors.lastname: Shin
keywords: Hepatitis C virus; Regulatory T cells; Ribavirin; Suppressive activity
references.citation: Curr Opin Virol. 2011 Dec;1(6):590-8
references.pmid: 22440916
references.citation: J Exp Med. 2007 Jun 11;204(6):1257-65
references.pmid: 17502665
references.citation: J Immunol. 2010 Jul 1;185(1):134-43
references.pmid: 20498355
references.citation: Science. 2008 Oct 10;322(5899):271-5
references.pmid: 18845758
references.citation: Br J Clin Pharmacol. 1998 Dec;46(6):563-70
references.pmid: 9862245
references.citation: N Engl J Med. 2002 Sep 26;347(13):975-82
references.pmid: 12324553
references.citation: J Exp Med. 2009 Feb 16;206(2):421-34
references.pmid: 19188497
references.citation: J Hepatol. 2000 Nov;33(5):791-8
references.pmid: 11097489
references.citation: Gastroenterology. 2010 Jul;139(1):154-62.e4
references.pmid: 20303352
references.citation: Virus Res. 2011 Apr;157(1):61-70
references.pmid: 21320556
references.citation: J Gastroenterol Hepatol. 2008 Aug;23(8 Pt 2):e432-7
references.pmid: 18248380
references.citation: Lancet. 2001 Sep 22;358(9286):958-65
references.pmid: 11583749
references.citation: J Med Virol. 2008 Sep;80(9):1523-9
references.pmid: 18649340
references.citation: PLoS One. 2012;7(7):e42094
references.pmid: 22848715
references.citation: Rev Med Virol. 2006 Jan-Feb;16(1):37-48
references.pmid: 16287208
references.citation: J Immunol. 2006 Oct 1;177(7):4376-83
references.pmid: 16982872
references.citation: Hepatology. 2011 Jan;53(1):32-41
references.pmid: 21254160
references.citation: J Hepatol. 1999 Mar;30(3):376-82
references.pmid: 10190717
references.citation: Liver Int. 2008 Dec;28(10):1332-43
references.pmid: 19055642
references.citation: Leuk Lymphoma. 2010 Oct;51(10):1805-15
references.pmid: 20629523
references.citation: N Engl J Med. 1986 Jan 2;314(1):20-6
references.pmid: 3940312
references.citation: Med Res Rev. 2008 Mar;28(2):219-32
references.pmid: 17480004