bcl-xL Is Critical for Dendritic Cell Survival In Vivo

• Published in: The Journal of immunology (1950) 2004-10, Vol.173 (7), p.4425-4432
• Main Authors: Hon, Huiming, Rucker, Edmund B., III, Hennighausen, Lothar, Jacob, Joshy
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Viral - biosynthesis; Apoptosis - genetics; Apoptosis - immunology; bcl-X Protein; Biolistics - methods; CD11c Antigen - biosynthesis; Cell Movement - genetics; Cell Movement - immunology; Cell Survival - genetics; Cell Survival - immunology; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Gene Silencing; Gene Targeting; Genetic Complementation Test; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Lymphocyte Activation - genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Orthomyxoviridae Infections - genetics; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - pathology; Protein Isoforms - deficiency; Protein Isoforms - genetics; Protein Isoforms - physiology; Proto-Oncogene Proteins c-bcl-2 - deficiency; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - physiology; RNA Interference - immunology; Vaccines, DNA - administration & dosage; Vaccines, DNA - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.173.7.4425

Dendritic cells (DC) are important regulators of immune function, transporting Ags from the periphery to draining lymph nodes (dLN) where they prime Ag-specific T lymphocytes. The magnitude of the immune response generated depends upon the longevity of the Ag-bearing DC in lymphoid tissues. We hypothesized that the control of DC survival is regulated by the antiapoptotic factor bcl-x(L). Gene gun immunization of dual-expression DNA vaccines into a bcl-x(fl/fl) mouse resulted in the delivery of Ag, as well as selective deletion of the bcl-x gene in directly transfected, skin-residing DC. bcl-x-deficient DC failed to mount effective immune responses, and this corresponded to their rapid disappearance from the dLN due to apoptosis. We confirmed these results using RNA interference to specifically silence the antiapoptotic bcl-x(L) isoform in targeted skin-residing DC of C57BL/6 mice. In addition, delivery of bcl-x(L) in trans complemented the bcl-x deficiency in DC of bcl-x(fl/fl) mice, resulting in the maintenance of normal levels of Ag-bearing DC in the dLN. Taken together, our work demonstrates that the bcl-x(L) isoform is critical for survival of skin-derived, Ag-bearing DC in vivo.