PMID- 11593031 OWN - NLM STAT- MEDLINE DCOM- 20011228 LR - 20181113 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 98 IP - 21 DP - 2001 Oct 9 TI - TNF-alpha -dependent maturation of local dendritic cells is critical for activating the adaptive immune response to virus infection. PG - 12162-7 AB - 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. FAU - Trevejo, J M AU - Trevejo JM AD - Department of Microbiology and Immunology, WJ Hearst Foundation, Weill Medical College of Cornell University, New York, NY 10021, USA. FAU - Marino, M W AU - Marino MW FAU - Philpott, N AU - Philpott N FAU - Josien, R AU - Josien R FAU - Richards, E C AU - Richards EC FAU - Elkon, K B AU - Elkon KB FAU - Falck-Pedersen, E AU - Falck-Pedersen E LA - eng GR - P01 HL051746/HL/NHLBI NIH HHS/United States GR - GM07739/GM/NIGMS NIH HHS/United States GR - GM18268/GM/NIGMS NIH HHS/United States GR - F31 GM018268/GM/NIGMS NIH HHS/United States GR - HL51746/HL/NHLBI NIH HHS/United States GR - T32 GM007739/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20011002 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Adaptation, Physiological/immunology MH - Adenoviridae Infections/*immunology MH - Adenoviruses, Human/immunology MH - Adoptive Transfer MH - Animals MH - B-Lymphocytes/immunology MH - Bone Marrow Cells/immunology MH - Cell Differentiation MH - Defective Viruses/immunology MH - Dendritic Cells/cytology/*immunology MH - Immunity, Active MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Knockout MH - T-Lymphocytes/immunology MH - Tumor Necrosis Factor-alpha/genetics/*immunology PMC - PMC59785 EDAT- 2001/10/11 10:00 MHDA- 2002/01/05 10:01 PMCR- 2002/04/09 CRDT- 2001/10/11 10:00 PHST- 2001/10/11 10:00 [pubmed] PHST- 2002/01/05 10:01 [medline] PHST- 2001/10/11 10:00 [entrez] PHST- 2002/04/09 00:00 [pmc-release] AID - 211423598 [pii] AID - 4235 [pii] AID - 10.1073/pnas.211423598 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12162-7. doi: 10.1073/pnas.211423598. Epub 2001 Oct 2.