期刊
JOURNAL OF INFECTIOUS DISEASES
卷 197, 期 1, 页码 46-57出版社
UNIV CHICAGO PRESS
DOI: 10.1086/523651
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资金
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK060590] Funding Source: NIH RePORTER
- NIDDK NIH HHS [R01 DK060590] Funding Source: Medline
- PHS HHS [U19 A 1066328-01] Funding Source: Medline
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 (T-reg) 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 T-reg 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 T-reg cell function. It is possible that repetitive viral antigenic stimulation alters the function of T-reg cells over time.
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