DNA immunization in vivo down-regulates nuclear all-trans retinoic acid receptors in mouse spleen cells

Nuclear retinoid receptors - retinoic acid inducible transcription factors - participate in pathways influencing many components of the immune system. In the present study in vivo effects of DNA-based immunization of mice on binding parameters of all-trans retinoic acid receptors (RARs) in spleen ce ll nuclei was investigated. A eucaryotic expression vector encoding the gen e for the model enzyme beta-galactosidase of Escherichia coli (pCMV-beta) w as used for intradermal injection. Furthermore, immunostimulatory CpG motif s, which stimulate the expression of various cytokines and may serve as a ' danger signal' for the mammalian immune system, were coinjected as oligodeo xynucleotides. The results demonstrate that the concentration of RARs was s ignificantly reduced in the late phase of the primary immune response (21 d ays after injection of plasmid DNA-indicated by high affinity IgG antibodie s and IFN-gamma expression). Coinjection of CpG motifs did not change the c ourse of the humoral response but enhanced and accelerated the proliferativ e response and expression of IFN-gamma, which correlated with the reduced R ARs concentration. (C) 2000 Elsevier Science Ireland Ltd. All rights reserv ed.