期刊
JOURNAL OF INFECTIOUS DISEASES
卷 203, 期 5, 页码 635-645出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiq101
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资金
- National Institutes of Health [R01 DK068361]
- National Institute on Alcohol Abuse and Alcoholism (NIAAA) [1F31AA017853]
Methods. Using flow cytometric analysis and enzyme-linked immunospot assay, we examined peripheral naive CD4 T cell phenotype and function in chronically HCV-infected patients and control subjects. Results. We observed significantly lower absolute cell numbers of naive CD4 T cells in HCV-infected patients, localized to the CD127(+)CD25(low/-) and CD31(+) (RTE) subsets. Moreover, we found greater percentages of naive cells expressing CD25 and KI67 in HCV-infected patients, consistent with immune activation, further supported by higher plasma sCD27 levels. Functional analysis revealed an intact interferon-gamma response to allogeneic B cell stimulus. However, after direct TCR stimulation, naive CD4 T cells from HCV-infected patients had altered up-regulation of KI67 and CD25 and less CD27 expression. The latter was associated with elevated baseline activation state. In addition, naive CD4 T cells from HCV-infected patients were more susceptible to cell death. Conclusions. These numerical and functional defects may contribute to inadequate formation of virus and neoantigen-specific T cell responses during chronic HCV infection.
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