Extrinsically derived TNF is primarily responsible for limiting antiviral CD8+ T cell response magnitude Academic Article uri icon

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.

authors

  • Quinn, KM
  • Kan, W-T
  • Watson, KA
  • Liddicoat, BJ
  • Swan, NG
  • McQuilten, H
  • Denton, AE
  • Li, J
  • Chen, Weisan
  • Brown, LE
  • Jackson, DC
  • Reading, PC
  • Doherty, PC
  • Kedzierska, K
  • Kedzierski, L
  • Turner, SJ
  • La Gruta, NL

publication date

  • 2017