4.8 Article

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

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.211423598

Keywords

-

Funding

  1. NHLBI NIH HHS [HL51746, P01 HL051746] Funding Source: Medline
  2. NIGMS NIH HHS [T32 GM007739, GM18268, F31 GM018268, GM07739] Funding Source: Medline

Ask authors/readers for more resources

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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available