Certain infections, like that with the human immunodeficiency virus‐1, deplete vitamin A, and when vitamin A levels are low, immune dysfunctions establish susceptibility to further infection. Our research has focused on the immune dysfunctions that are a consequence of vitamin A deficiency and that predispose to further infection. We previously studied a helminth infection in mice, and showed that when vitamin A levels are low, the immune response develops a strong regulatory T cell imbalance with excessive T helper type‐1 cell interferon (IFN)‐γ synthesis and insufficient T helper type‐2 cell development and function. Here, we studied the T cell priming environment in vitamin A‐deficient mice to learn how that priming environment might produce a regulatory T cell imbalance and consequently distort the ability of the immune system to respond to an infection. Our results show that during vitamin A deficiency, the priming environment included constitutive interleukin (IL)‐12 and IFN‐γ transcripts, but it was devoid of constitutive IL‐4 and IL‐10 transcripts. Dietary all‐trans‐retinoic acid supplementation down‐regulated the level of constitutive IL‐12 and IFN‐γ transcripts. Furthermore, when T cells from naive vitamin A‐deficient animals were stimulated through the T cell receptor, they produced excess IFN‐γ protein compared to T cells from control animals. In contrast, T cell stimulation failed to induce IL‐4 or IL‐10 secretion. The inducible IFN‐γ was largely from CD8+ T cells and all‐trans‐retinoic acid addition in vitro inhibited IFN‐γ production at the transcript level. Retinoic acid addition in vitro also decreased natural killer cell IFN‐γ synthesis at the transcript level. Taken together, the distorted constitutive and inducible cytokine gene expression patterns that occurred when vitamin A levels were low would be expected strongly to favor T helper type‐1 development and limit T helper type‐2 cell growth and differentiation, thereby limiting the animal's humoral immune response capability.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy