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* Department of Microbiology and Immunology, Emory Vaccine Center, Emory University, Atlanta, GA 30329;
Department of Animal Sciences, University of Missouri, Columbia, MO 65211; and
Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892
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-xL. Gene gun immunization of dual-expression DNA vaccines into a bcl-xfl/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-xL isoform in targeted skin-residing DC of C57BL/6 mice. In addition, delivery of bcl-xL in trans complemented the bcl-x deficiency in DC of bcl-xfl/fl mice, resulting in the maintenance of normal levels of Ag-bearing DC in the dLN. Taken together, our work demonstrates that the bcl-xL isoform is critical for survival of skin-derived, Ag-bearing DC in vivo.
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