Rapid early innate control of hepatitis C virus during IFN-α treatment compromises adaptive CD4+T-cell immunity

Pembroke, Thomas ORCID: https://orcid.org/0000-0002-2600-2034, Rees, Ian W., Gallagher, Kathleen, Jones, Emma, Mizen, Paul Edward, Navruzov, Timur, Freedman, Andrew Robert, Fielding, Ceri Alan ORCID: https://orcid.org/0000-0002-5817-3153, Humphreys, Ian R. ORCID: https://orcid.org/0000-0002-9512-5337, Wang, Edward Chung Yern ORCID: https://orcid.org/0000-0002-2243-4964, Gallimore, Awen Myfanwy ORCID: https://orcid.org/0000-0001-6675-7004 and Godkin, Andrew James ORCID: https://orcid.org/0000-0002-1910-7567 2012. Rapid early innate control of hepatitis C virus during IFN-α treatment compromises adaptive CD4+T-cell immunity. European Journal of Immunology 42 (9) , pp. 2383-2394. 10.1002/eji.201142072

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Abstract

The ability to control HCV with IFN-α-based treatments provides an opportunity in humans to study how the rate of viral clearance in vivo impinges on the development of antiviral responses. Ex vivo (IFN-γ-producing) and cultured antiviral CD4+ T cells, serum cytokines, and viral loads were measured repeatedly in a cohort of chronically HCV-infected subjects (n = 33) receiving IFN-α. Rapid control of virus indicated by an increased calculated rate of virus clearance, occurred in those subjects demonstrating absent/minimal T-cell responses (p < 0.0006). Surprisingly, in subjects who demonstrated the most robust T-cell responses (and reduced serum IL-10), there was actually a reduced rate of early virus clearance. A subsequent analysis of NK-cell function in available subjects (n = 8) revealed an inverse correlation between pretreatment NK-cell expression of NKp46 and the potential to upregulate cytotoxic function on exposure to IFN-α (p < 0.004), as well as the subsequent measured rate of viral clearance (p = 0.045). Thus, the CD4+ T-cell response during IFN-α treatment appears to be shaped by the rate of innate virus suppression. These data suggest that individuals who respond most effectively to immune intervention may be most in need of subsequent vaccination to prevent reinfection.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR180 Immunology R Medicine > R Medicine (General)
Uncontrolled Keywords:	CD4+ T cells; Hepatitis C virus; IFN-α; NK cells
Publisher:	John Wiley & Sons
ISSN:	0014-2980
Last Modified:	21 Oct 2022 10:49
URI:	https://orca.cardiff.ac.uk/id/eprint/41450

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