Vitamin A deficiency results in a priming environment conducive for Th1 cell development

Margherita Teresa-Anna Cantorna, Faye E. Nashold, Colleen E. Hayes

Research output: Contribution to journalArticle

112 Citations (Scopus)

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)‐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.

Original languageEnglish (US)
Pages (from-to)1673-1679
Number of pages7
JournalEuropean Journal of Immunology
Volume25
Issue number6
DOIs
StatePublished - Jan 1 1995

Fingerprint

Vitamin A Deficiency
Th1 Cells
Interferons
Vitamin A
T-Lymphocytes
Infection
Regulatory T-Lymphocytes
Interleukin-12
Helper-Inducer T-Lymphocytes
Vitamins
Interleukin-4
Interleukin-10
Acids
Helminths
Humoral Immunity
T-Cell Antigen Receptor
Tretinoin
Natural Killer Cells
Cell Differentiation
Immune System

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

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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)‐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.",
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Vitamin A deficiency results in a priming environment conducive for Th1 cell development. / Cantorna, Margherita Teresa-Anna; Nashold, Faye E.; Hayes, Colleen E.

In: European Journal of Immunology, Vol. 25, No. 6, 01.01.1995, p. 1673-1679.

Research output: Contribution to journalArticle

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