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PMID: 11593031 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 98 ·No. 21 ·2001-10-09 ·Pages 12162-7

Trevejo JM, Marino MW, Philpott N, Josien R, Richards EC, Elkon KB, Falck-Pedersen E

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.

MeSH Terms
Adaptation, Physiological/immunology Adenoviridae Infections/immunology Adenoviruses, Human/immunology Adoptive Transfer Animals B-Lymphocytes/immunology Bone Marrow Cells/immunology Cell Differentiation Defective Viruses/immunology Dendritic Cells/cytology,immunology Immunity, Active Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout T-Lymphocytes/immunology Tumor Necrosis Factor-alpha/genetics,immunology
Chemicals
Tumor Necrosis Factor-alpha
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Trevejo J M
Department of Microbiology and Immunology, WJ Hearst Foundation, Weill Medical College of Cornell University, New York, NY 10021, USA.
Marino M W
Philpott N
Josien R
Richards E C
Elkon K B
Falck-Pedersen E
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.211423598
Published
2001-10-09
Epub
2001-00-02
Pages
12162-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC59785
Subset
IM
Grants
NHLBI NIH HHS · P01 HL051746 · United States
NIGMS NIH HHS · GM07739 · United States
NIGMS NIH HHS · GM18268 · United States
NIGMS NIH HHS · F31 GM018268 · United States
NHLBI NIH HHS · HL51746 · United States
NIGMS NIH HHS · T32 GM007739 · United States
External Links
PubMed source DOI: 10.1073/pnas.211423598 PMC Full Text View journal details
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