Format

Send to

Choose Destination
PLoS One. 2017 Sep 8;12(9):e0184732. doi: 10.1371/journal.pone.0184732. eCollection 2017.

Extrinsically derived TNF is primarily responsible for limiting antiviral CD8+ T cell response magnitude.

Author information

1
Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
2
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia.
3
T cell laboratory, School of Molecular Sciences, La Trobe University, Bundoora, Victoria, Australia.
4
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, United States of America.
5
Faculty of Veterinary and Agricultural Sciences, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia.

Abstract

TNF is a pro-inflammatory cytokine produced by both lymphoid and non-lymphoid cells. As a consequence of the widespread expression of its receptors (TNFR1 and 2), TNF plays a role in many important biological processes. In the context of influenza A virus (IAV) infection, TNF has variably been implicated in mediating immunopathology as well as suppression of the immune response. Although a number of cell types are able to produce TNF, the ability of CD8+ T cells to produce TNF following viral infection is a hallmark of their effector function. As such, the regulation and role of CD8+ T cell-derived TNF following viral infection is of great interest. Here, we show that the biphasic production of TNF by CD8+ T cells following in vitro stimulation corresponds to distinct patterns of epigenetic modifications. Further, we show that a global loss of TNF during IAV infection results in an augmentation of the peripheral virus-specific CD8+ T cell response. Subsequent adoptive transfer experiments demonstrated that this attenuation of the CD8+ T cell response was largely, but not exclusively, conferred by extrinsic TNF, with intrinsically-derived TNF making only modest contributions. In conclusion, TNF exerts an immunoregulatory role on CD8+ T cell responses following IAV infection, an effect that is largely mediated by extrinsically-derived TNF.

PMID:
28886201
PMCID:
PMC5590991
DOI:
10.1371/journal.pone.0184732
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center