Document 0829
 DOCN  M95A0829
 TI    Vitamin A deficiency results in a priming environment conducive for Th1
       cell development.
 DT    9510
 AU    Cantorna MT; Nashold FE; Hayes CE; Department of Biochemistry,
       University of Wisconsin-Madison; 53706, USA.
 SO    Eur J Immunol. 1995 Jun;25(6):1673-9. Unique Identifier : AIDSLINE
       MED/95339883
 AB    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.
 DE    Animal  Cell Differentiation  Cells, Cultured  Diet  Down-Regulation
       (Physiology)  Interferon Type II/ANTAGONISTS & INHIB/*BIOSYNTHESIS
       Interleukin-12/ANTAGONISTS & INHIB/*BIOSYNTHESIS  Mice  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  T-Lymphocytes,
       Helper-Inducer/*IMMUNOLOGY  Transcription, Genetic
       Tretinoin/*ADMINISTRATION & DOSAGE  Vitamin A Deficiency/*IMMUNOLOGY
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).