Type I interferon suppresses de novo virus-specific CD4 Th1 immunity during an established persistent viral infection
Open Access
- 5 May 2014
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 111 (20), 7409-7414
- https://doi.org/10.1073/pnas.1401662111
Abstract
CD4 T cells are central to orchestrate, sustain, and potentially regenerate antiviral immunity throughout persistent viral infections. Although the evolving immune environment during persistent infection reshapes established CD4 T-cell responses, the fate of naïve CD4 T cells primed in the midst of persistent infection is unclear. We demonstrate that, in marked contrast to the onset of infection, virus-specific CD4 T cells primed during an established persistent infection have diminished ability to develop Th1 responses, to efficiently accumulate in peripheral tissues, and almost exclusively differentiate into T follicular helper cells. Consistent with suppressed Th1 and heightened Tfh differentiation, virus-specific CD4 T cells primed during the established persistent infection provide help to B cells, but only limited help to CD8 T cells. The suppression of de novo Th1 generation and tissue distribution was mediated by chronic type I IFN (IFN-I) production and was effectively restored by blocking IFN-I signaling during CD4 T-cell priming. Thus, we establish a suppressive function of chronic IFN-I signaling and mechanism of immunoregulation during an established persistent virus infection.Keywords
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