title: Retinoic acid enhances the T helper 2 cell development that is essential for robust antibody responses through its action on antigen-presenting cells.
abstract: Previously we reported that vitamin A-deficient (-A) mice had a profound reduction in T helper 2 (Th2) cells, accounting for their depressed T-dependent antibody responses. Providing vitamin A or its active metabolites reversed this defect. The current experiments utilized splenocytes from T cell receptor transgenic mice to investigate how all-trans retinoic acid (atRA) augments Th2 development. These cells were stimulated in vitro in the presence or absence of atRA, with or without exogenous cytokines driving Th1 or Th2 development. Without exogenous cytokines, atRA addition significantly inhibited the interferon (IFN)-gamma response but did not alter the interleukin (IL)-4 response. With Th1 polarizing cytokines, atRA enhanced the IFN-gamma response, with no effect on the IL-4 response. Most importantly, with the Th2 polarizing cytokine IL-4, atRA significantly increased the IL-4 secretion (fivefold) and also increased the Th2 cell frequency twofold. The striking Th2 enhancement was also observed when only antigen-presenting cells were treated with atRA before stimulation of untreated CD4(+) transgenic T cells, but not vice versa. Thus, atRA maximized Th2 cell development in an IL-4-dependent manner, through an effect on antigen-presenting cell function.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, 53706, USA. hoagk@msu.edu
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Hoag
authors.forename: Faye E
authors.initials: FE
authors.lastname: Nashold
authors.forename: Joan
authors.initials: J
authors.lastname: Goverman
authors.forename: Colleen E
authors.initials: CE
authors.lastname: Hayes
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D005455:Fluorescent Antibody Technique; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D015847:Interleukin-4; D014212:Tretinoin