Retinoic acid and polyriboinosinic acid act synergistically to enhance theantibody response to tetanus toxoid during vitamin A deficiency: Possible involvement of interleukin-2 receptor-beta, signal transducer and activatorof transcription-1, and interferon regulatory factor-1

Antibody responses to T cell-dependent antigens are reduced during vitamin A (VA) deficiency and restored by retinoids. To test whether retinoic acid (RA) and polyinosinic:polycytidylic acid (PIC), an inducer of interferons, can increase specific antibody production, VA-deficient rats were treated w ith all-trans-RA, PIG, or both at the time of primary immunization with tet anus toroid. VA-deficient rats produced low primary and secondary antitetan us IgG responses (P<.001 vs. VA-sufficient controls). Both responses were i ncreased synergistically by RA plus PIC (P<.0001). In VA-deficient spleens, mRNAs were low for interleukin (IL)-2 receptor-beta, interferon regulatory factor-1, and signal transducer and activator of transcription 1. Each, ho wever, was induced by RA plus PIC (P <.0001 vs. controls). Conversely, IL-1 2 and IL-10 mRNAs were elevated in VA deficiency and were induced by PIC an d suppressed by RA. Thus, RA plus PIC appears to be a promising combination for stimulating antigen-specific immunity. Several molecular factors ident ified here may partially account for the observed enhancement.