Retinoic acid repletion restores the number of leukocytes and their subsets and stimulates natural cytotoxicity in vitamin A-deficient rats

Previously we reported that vitamin A-deficient rats have a low number of natural killer (NK) cells in their blood and spleen. The current studies were designed to address whether other cells of the immune system are also affected and whether dietary retinoic acid is able to reverse the changes caused by a deficiency of retinol and its metabolites. Total white blood cells, differential counts and spleen cell numbers were compared in vitamin A-sufficient rats (controls) and rats deficient in vitamin A, and lymphocyte and NK cell populations were identified and enumerated by flow cytometry. In comparison with control rats, the blood of deficient rats had three times the number of granulocytes, and fewer B lymphocytes (73% of control) and NK cells (38% of control). The numbers of splenic B, cells (OX12⁺), CD5⁺ (OX19⁺) and CD4⁺ (W3/25⁺) T lymphocytes and NK cells (HKR-P1⁺) were also significantly reduced. When vitamin A-deficient rats were fed a retinoic acid supplement (4.2 mg all-trans retinoic acid/kg diet) for 28 d, the numbers of blood granulocytes and NK cells equaled those of control rats and HK cell cytotoxicity was significantly elevated. Blood lymphocyte number was increased 40% due to increases of B cells and T cells of the CD5⁺, CD4⁺ and CD8⁺ subsets. These data indicate that vitamin A deficiency affects a number of cells of the immune system and that repletion with retinoic acid effectively reestablishes the number of circulating lymphocytes. In addition, retinoic acid may stimulate NK cell function.