Hepatitis C virus specific CD4+ T cell phenotype and function in different infection outcomes
- 3 February 2020
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 130 (2), 768-773
- https://doi.org/10.1172/JCI126277
Abstract
CD4(+) T cell failure is a hallmark of chronic hepatitis C virus (HCV) infection. However, the mechanisms underlying the impairment and loss of virus-specific CD4(+) T cells in persisting HCV infection remain unclear. Here we examined HCV-specific CD4(+) T cells longitudinally during acute infection with different infection outcomes. We found that HCV-specific CD4(+) T cells are characterized by expression of a narrower range of T cell inhibitory receptors compared with CD8(+) T cells, with initially high expression levels of PD-1 and CTLA-4 that were associated with negative regulation of proliferation in all patients, irrespective of outcome. In addition, HCV-specific CD4(+) T cells were phenotypically similar during early resolving and persistent infection and secreted similar levels of cytokines. However, upon viral control, CD4(+) T cells quickly downregulated inhibitory receptors and differentiated into long-lived memory cells. In contrast, persisting viremia continued to drive T cell activation and PD-1 and CTLA-4 expression, and blocked T cell differentiation, until the cells quickly disappeared from the circulation. Our data support an important and physiological role for inhibitory receptor-mediated regulation of CD4(+) T cells in early HCV infection, irrespective of outcome, with persistent HCV viremia leading to sustained upregulation of PD-1 and CTLA-4.Funding Information
- National Institutes of Health (R01 AI105035)
- National Institutes of Health (U01 AI131314)
- National Institutes of Health (U19 AI086230)
- National Institutes of Health (R01 DA046277)
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