본문 바로가기
KERD
논문KCI 등재

Ribavirin Does Not Impair the Suppressive Activity of Foxp3+CD4+CD25+ Regulatory T Cells

1

조회

0

다운로드

0

인용

0

참고문헌

키워드

초록

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.

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.

참고문헌 (22)

  1. Manns, M. P., "Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial", Lancet, 358, pp.958~965 (2001)
  2. Fried, M. W., "Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection", N. Engl. J. Med, 347, pp.975~982 (2002)
  3. Borden, K. L., "Ribavirin as an anti-cancer therapy: acute myeloid leukemia and beyond? Leuk", Lymphoma, 51, pp.1805~1815 (2010)
  4. McCormick, J. B., "Lassa fever. Effective therapy with ribavirin", N. Engl. J. Med, 314, pp.20~26 (1986)
  5. Paeshuyse, J., "Ribavirin for the treatment of chronic hepatitis C virus infection: a review of the proposed mechanisms of action", Curr. Opin. Virol, 1, pp.590~598 (2011)
  6. Mori, K., "Mechanism of action of ribavirin in a novel hepatitis C virus replication cell system", Virus. Res, 157, pp.61~70 (2011)
  7. Shu, Q., "Inosine monophosphate dehydrogenase (IMPDH) as a target in drug discovery", Med. Res. Rev, 28, pp.219~232 (2008)
  8. Graci, J. D., "Mechanisms of action of ribavirin against distinct viruses", Rev. Med. Virol, 16, pp.37~48 (2006)
  9. Feld, J. J., "Ribavirin improves early responses to peginterferon through improved interferon signaling", Gastroenterology, 139, pp.154~162 (2010)
  10. Thomas, E., "Ribavirin potentiates interferon action by augmenting interferon-stimulated gene induction in hepatitis C virus cell culture models", Hepatology, 53, pp.32~41 (2011)
  11. Tam, R. C., "Ribavirin polarizes human T cell responses towards a Type 1 cytokine profile", J. Hepatol, 30, pp.376~382 (1999)
  12. Fang, S. H., "Ribavirin enhancement of hepatitis C virus core antigen- specific type 1 T helper cell response correlates with the increased IL-12 level", J. Hepatol, 33, pp.791~798 (2000)
  13. Fujimoto, T., "Changes in the Th1", Th2 ratio during a 24-week course of an interferon alpha-2b plus ribavirin combination therapy for patients with chronic hepatitis C, 2008, pp.23, e432~e437
  14. Hofmann, W. P., "Ribavirin mode of action in chronic hepatitis C: from clinical use back to molecular mechanisms", Liver Int, 28, pp.1332~1343 (2008)
  15. Langhans, B., "Ribavirin exerts differential effects on functions of Cd4+ Th1, Th2, and regulatory T cell clones in hepatitis C", PLoS One, 7, pp.e42094~ (2012)
  16. Khakoo, S., "Ribavirin and interferon alfa-2b in chronic hepatitis C: assessment of possible pharmacokinetic and pharmacodynamic interactions", Br. J. Clin. Pharmacol, 46, pp.563~570 (1998)
  17. Nicot, F., "Serum concentrations of ribavirin and pegylated interferon and viral responses in patients infected with HIV and HCV", J. Med. Virol, 80, pp.1523~1529 (2008)
  18. Read, S., "Blockade of CTLA-4 on CD4+CD25+ regulatory T cells abrogates their function in vivo", J. Immunol, 177, pp.4376~4383 (2006)
  19. Wing, K., "CTLA-4 control over Foxp3+ regulatory T cell function", Science, 322, pp.271~275 (2008)
  20. Friedline, R. H., "CD4+ regulatory T cells require CTLA-4 for the maintenance of systemic tolerance", J. Exp. Med, 206, pp.421~434 (2009)
  21. Deaglio, S., "Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression", J. Exp. Med, 204, pp.1257~1265 (2007)
  22. Moncrieffe, H., "High expression of the ectonucleotidase CD39 on T cells from the inflamed site identifies two distinct populations, one regulatory and one memory T cell population", J. Immunol, 185, pp.134~143 (2010)

관련 논문AI추천

이 간행물의 다른 논문 (5건)