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

TitleTNF-alpha -dependent maturation of local dendritic cells is critical for activating the adaptive immune response to virus infection.
Publication TypeJournal Article
Year of Publication2001
AuthorsTrevejo JM, Marino MW, Philpott N, Josien R, Richards EC, Elkon KB, Falck-Pedersen E
JournalProc Natl Acad Sci U S A
Volume98
Issue21
Pagination12162-7
Date Published2001 Oct 09
ISSN0027-8424
KeywordsAdaptation, Physiological, Adenoviridae Infections, Adenoviruses, Human, Adoptive Transfer, Animals, B-Lymphocytes, Bone Marrow Cells, Cell Differentiation, Defective Viruses, Dendritic Cells, Immunity, Active, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, T-Lymphocytes, 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.

DOI10.1073/pnas.211423598
Alternate JournalProc Natl Acad Sci U S A
PubMed ID11593031
PubMed Central IDPMC59785
Grant ListP01 HL051746 / HL / NHLBI NIH HHS / United States
GM07739 / GM / NIGMS NIH HHS / United States
GM18268 / GM / NIGMS NIH HHS / United States
F31 GM018268 / GM / NIGMS NIH HHS / United States
HL51746 / HL / NHLBI NIH HHS / United States
T32 GM007739 / GM / NIGMS NIH HHS / United States

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