Retinoic Acid and Polyriboinosinic Acid Act Synergistically to Enhance the Antibody Response to Tetanus Toxoid during Vitamin A Deficiency: Possible Involvement of Interleukin‐2 Receptor‐β, Signal Transducer and Activator of Transcription‐1, and Interferon Regulatory Factor‐1

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Abstract
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 with all-trans-RA, PIC, or both at the time of primary immunization with tetanus toxoid. VA-deficient rats produced low primary and secondary anti-tetanus IgG responses (P <.001 vs. VA-sufficient controls). Both responses were increased synergistically by RA plus PIC (P < .0001). In VA-deficient spleens, mRNAs were low for interleukin (IL)-2 receptor-β, interferon regulatory factor-1, and signal transducer and activator of transcription 1. Each, however, was induced by RA plus PIC (P < .0001 vs. controls). Conversely, IL-12 and IL-10 mRNAs were elevated in VA deficiency and were induced by PIC and suppressed by RA. Thus, RA plus PIC appears to be a promising combination for stimulating antigen-specific immunity. Several molecular factors identified here may partially account for the observed enhancement.