Title | TNF-alpha -dependent maturation of local dendritic cells is critical for activating the adaptive immune response to virus infection. |
Publication Type | Journal Article |
Year of Publication | 2001 |
Authors | Trevejo JM, Marino MW, Philpott N, Josien R, Richards EC, Elkon KB, Falck-Pedersen E |
Journal | Proc Natl Acad Sci U S A |
Volume | 98 |
Issue | 21 |
Pagination | 12162-7 |
Date Published | 2001 Oct 09 |
ISSN | 0027-8424 |
Keywords | Adaptation, 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. |
DOI | 10.1073/pnas.211423598 |
Alternate Journal | Proc Natl Acad Sci U S A |
PubMed ID | 11593031 |
PubMed Central ID | PMC59785 |
Grant List | P01 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 |
Submitted by jom4013 on December 3, 2020 - 4:11pm