title: Oral tolerance and TGF-beta-producing cells.
abstract: Multiple mechanisms have been proposed to explain the immune hyporesponsiveness to fed antigens, a phenomenon named oral tolerance. Low doses of orally administered antigen are reported to favor active suppression with the generation of regulatory cells, whereas high doses would favor clonal anergy/deletion. A major conceptual advance in oral tolerance has been the demonstration that TGF-beta plays a central role in oral tolerance as a mediator secreted by Th3 cells. In addition, recent pieces of evidence suggest that TGF-beta may be a primary link between distinct populations of regulatory T cells that are induced by feeding. Conversion of CD4+CD25- into CD4+CD25+ T cells by the expression of FoxP3 involves TGF-beta. A membrane-bound form of TGF-beta (containing latency-associated peptide - LAP) has also been described and LAP+ CD4+ T cells mediate suppression in the gut by a TGF-beta-dependent mechanism. Most of these regulatory T cells are anergic cells indicating that anergy may be also related to Treg induction. Moreover, deletional events taking place in the gut mucosa induce TGF-beta production by either macrophages that phagocyte apoptotic cells or by the dying T cells. Thus, it appears that TGF-beta-producing cells are not only crucial for oral tolerance, but they may be master regulators of most of the mechanisms triggered by antigen feeding.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur Him 730, Boston, MA 02115, USA. afaria@icb.ufmg.br
authors.forename: Ana M C
authors.initials: AM
authors.lastname: Faria
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology
chemical_list: D000941:Antigens; D016212:Transforming Growth Factor beta