Functional suppression by FoxP3+CD4+CD25 high regulatory T cells during acute hepatitis C virus infection

Susan Smyk-Pearson, Lucy Golden-Mason, Jared Klarquist, James R. Burton, Ian A. Tester, Chia C. Wang, Nicole Culbertson, Arthur Vandenbark, Hugo R. Rosen

Research output: Contribution to journalArticle

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Abstract

Background. Infection with hepatitis C virus (HCV) is characterized by impairment of viral effector T cell responses and a high propensity for viral persistence. Previous studies have demonstrated that chronic HCV infection is associated with an increased frequency of regulatory T (Treg) cells, compared with that in persons whose infection resolved and in healthy persons. However, all patients in prior analyses had exposures in the distant past, precluding the ability to determine whether Treg cells play a causal role in establishing persistence during the earliest stages of infection or whether they are expanded because of viral persistence. Methods. For the first time, we longitudinally analyzed Treg cells in patients with acute HCV infection (n = 27). We used a multiparameter approach, including fluorescence-activated cell sorting analysis of cell-surface and intracellular antigens, coculture experiments with highly purified CD4+CD25 high regulatory and CD4+CD25- responder cell populations, and multiplex analysis of secreted cytokines. Results. Forkhead transcription factor 3 (FoxP3) expression and Treg cell suppression were greater in patients with acute HCV infection than in healthy control subjects but were not different at the first time point among patients who subsequently developed persistence or resolved HCV infection spontaneously; however, 6 months later, the resolution of disease was associated with a relative loss of functional suppression. Conclusions. Collectively, these data indicate that patients with acute HCV infection who develop chronicity versus spontaneous resolution exhibit temporal changes in Treg cell function. It is possible that repetitive viral antigenic stimulation alters the function of Treg cells over time.

Original languageEnglish (US)
Pages (from-to)46-57
Number of pages12
JournalJournal of Infectious Diseases
Volume197
Issue number1
DOIs
StatePublished - Jan 1 2008

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Virus Diseases
Regulatory T-Lymphocytes
Hepacivirus
Infection
Transcription Factor 3
Forkhead Transcription Factors
Chronic Hepatitis C
Surface Antigens
Coculture Techniques
Healthy Volunteers
Flow Cytometry
Cytokines
T-Lymphocytes
Population

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Smyk-Pearson, S., Golden-Mason, L., Klarquist, J., Burton, J. R., Tester, I. A., Wang, C. C., ... Rosen, H. R. (2008). Functional suppression by FoxP3+CD4+CD25 high regulatory T cells during acute hepatitis C virus infection. Journal of Infectious Diseases, 197(1), 46-57. https://doi.org/10.1086/523651

Functional suppression by FoxP3+CD4+CD25 high regulatory T cells during acute hepatitis C virus infection. / Smyk-Pearson, Susan; Golden-Mason, Lucy; Klarquist, Jared; Burton, James R.; Tester, Ian A.; Wang, Chia C.; Culbertson, Nicole; Vandenbark, Arthur; Rosen, Hugo R.

In: Journal of Infectious Diseases, Vol. 197, No. 1, 01.01.2008, p. 46-57.

Research output: Contribution to journalArticle

Smyk-Pearson, S, Golden-Mason, L, Klarquist, J, Burton, JR, Tester, IA, Wang, CC, Culbertson, N, Vandenbark, A & Rosen, HR 2008, 'Functional suppression by FoxP3+CD4+CD25 high regulatory T cells during acute hepatitis C virus infection', Journal of Infectious Diseases, vol. 197, no. 1, pp. 46-57. https://doi.org/10.1086/523651
Smyk-Pearson S, Golden-Mason L, Klarquist J, Burton JR, Tester IA, Wang CC et al. Functional suppression by FoxP3+CD4+CD25 high regulatory T cells during acute hepatitis C virus infection. Journal of Infectious Diseases. 2008 Jan 1;197(1):46-57. https://doi.org/10.1086/523651
Smyk-Pearson, Susan ; Golden-Mason, Lucy ; Klarquist, Jared ; Burton, James R. ; Tester, Ian A. ; Wang, Chia C. ; Culbertson, Nicole ; Vandenbark, Arthur ; Rosen, Hugo R. / Functional suppression by FoxP3+CD4+CD25 high regulatory T cells during acute hepatitis C virus infection. In: Journal of Infectious Diseases. 2008 ; Vol. 197, No. 1. pp. 46-57.
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