title: Vitamin A deficiency results in a priming environment conducive for Th1 cell development.
abstract: 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)-gamma 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-gamma 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-gamma transcripts. Furthermore, when T cells from naive vitamin A-deficient animals were stimulated through the T cell receptor, they produced excess IFN-gamma 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-gamma was largely from CD8+ T cells and all-trans-retinoic acid addition in vitro inhibited IFN-gamma production at the transcript level. Retinoic acid addition in vitro also decreased natural killer cell IFN-gamma 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.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison 53706, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Cantorna
authors.forename: F E
authors.initials: FE
authors.lastname: Nashold
authors.forename: C E
authors.initials: CE
authors.lastname: Hayes
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004032:Diet; D015536:Down-Regulation; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051379:Mice; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014158:Transcription, Genetic; D014212:Tretinoin / Q000008:administration & dosage*; D014802:Vitamin A Deficiency / Q000276:immunology*
chemical_list: D018664:Interleukin-12; D014212:Tretinoin; D007371:Interferon-gamma