Extrinsically derived TNF is primarily responsible for limiting antiviral CD8+T cell response magnitude
AuthorQuinn, KM; Kan, W-T; Watson, KA; Liddicoat, BJ; Swan, NG; McQuilten, H; Denton, AE; Li, J; Chen, W; Brown, LE; ...
Source TitlePLoS One
PublisherPUBLIC LIBRARY SCIENCE
University of Melbourne Author/sLa Gruta, Nicole; Reading, Patrick; Doherty, Peter; Kedzierska, Katherine; KAN, WAN-TING; WATSON, KATHERINE; SWAN, NATASHA; McQuilten, Hayley; Brown, Lorena; Jackson, David; ...
AffiliationMicrobiology and Immunology
Veterinary and Agricultural Sciences
Document TypeJournal Article
CitationsQuinn, K. M., Kan, W. -T., Watson, K. A., Liddicoat, B. J., Swan, N. G., McQuilten, H., Denton, A. E., Li, J., Chen, W., Brown, L. E., Jackson, D. C., Reading, P. C., Doherty, P. C., Kedzierska, K., Kedzierski, L., Turner, S. J. & La Gruta, N. L. (2017). Extrinsically derived TNF is primarily responsible for limiting antiviral CD8+T cell response magnitude. PLOS ONE, 12 (9), https://doi.org/10.1371/journal.pone.0184732.
Access StatusOpen Access
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.
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