TNF-α-dependent maturation of local dendritic cells is critical for activating the adaptive immune response to virus infection Academic Article uri icon

Overview

MeSH Major

  • Adenoviridae Infections
  • Dendritic Cells
  • Tumor Necrosis Factor-alpha

abstract

  • Tumor necrosis factor-alpha (TNF-alpha) is well recognized for its role in mediating innate immune responses. However, the mechanisms of TNF-alpha that influence the adaptive immune response to virus infections are not well understood. In this study, we have investigated the role of TNF-alpha in activating the cellular and humoral responses to systemic viral challenge with recombinant replication-defective adenovirus (rAd). Evaluation of T cell function in TNF-alpha-deficient (TNFKO) mice revealed impaired virus-specific proliferation of T cells derived from the draining lymph nodes of the liver. Analysis of dendritic cells (DC) isolated from local draining lymph nodes after systemic challenge showed that DC from TNFKO mice were relatively immature compared with those from strain-matched wild-type mice. In vitro, TNF-alpha was required to mature DC efficiently during virus-mediated stimulation. Adoptive transfer of primed, mature DC into TNFKO mice restored T cell responses and reconstituted anti-adenovirus antibody responses. Thus, TNF-alpha plays a significant role in the maturation of DC after adenovirus challenge both in vitro and in vivo, highlighting the importance of this innate cytokine in activating adaptive immunity to viral challenge.

publication date

  • October 9, 2001

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC59785

Digital Object Identifier (DOI)

  • 10.1073/pnas.211423598

PubMed ID

  • 11593031

Additional Document Info

start page

  • 12162

end page

  • 7

volume

  • 98

number

  • 21