title: Dysfunction of CD4+CD25high T regulatory cells in patients with recurrent aphthous stomatitis.
abstract: BACKGROUND
  Recurrent aphthous stomatitis (RAS) is a chronic inflammatory disease of unknown etiology characterized by recurring formation of painful oral ulcers. RAS may result from oral epithelium damage caused by T-cell-mediated immune response. CD4(+)CD25(+) T regulatory (Treg) cells suppress proliferation and effector functions of other immune cells, and therefore are crucial in regulating the immune response.
  
  
  METHODS
  We tested the function of peripheral CD4(+)CD25(high) Treg cells in active RAS through their ability to inhibit proliferation and cytokine production of conventional CD4(+) T cells. We also attempted to detect the presence of FOXP3 and indoleamine 2,3-dioxygenase (IDO) mRNA in the lesional and non-lesional oral mucosa of RAS patients and healthy individuals using real-time PCR assay.
  
  
  RESULTS
  Treg cells derived from RAS patients were less efficient in the suppression of cytokine production of CD4(+) T effector cells than Treg cells from healthy individuals. Moreover, in RAS, Treg cells were nearly twice less potent in the inhibition of CD4(+)CD25(-) T cell proliferation than in healthy donors. Furthermore, we have demonstrated the decreased proportion of CD4(+)CD25(+)FOXP3(+) Treg cells in peripheral blood of RAS patients compared with controls. We failed to detect FOXP3 mRNA, while IDO mRNA expression was decreased in non-lesional mucosa biopsies from RAS patients compared with ulcer biopsies or normal mucosa from healthy donors.
  
  
  CONCLUSIONS
  These findings suggest that CD4(+)CD25(high) Treg cells are both functionally and quantitatively compromised in RAS and that decreased constitutive expression of IDO in oral mucosa in RAS may lead to the loss of local immune tolerance.
authors.affiliation: Department of Periodontology and Oral Medicine, Medical University of Lodz, Lodz, Poland. natalewk@wp.pl
authors.forename: Natalia
authors.initials: N
authors.lastname: Lewkowicz
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Lewkowicz
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Dzitko
authors.forename: Barabara
authors.initials: B
authors.lastname: Kur
authors.forename: Maciej
authors.initials: M
authors.lastname: Tarkowski
authors.forename: Anna
authors.initials: A
authors.lastname: Kurnatowska
authors.forename: Henryk
authors.initials: H
authors.lastname: Tchórzewski
mesh_terms: D000328:Adult; D001706:Biopsy; D015704:CD4 Antigens / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000032:analysis; D007371:Interferon-gamma / Q000032:analysis; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D007378:Interleukins / Q000032:analysis; D008297:Male; D009061:Mouth Mucosa / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012008:Recurrence; D013281:Stomatitis, Aphthous / Q000097:blood / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053645:Interleukin-2 Receptor alpha Subunit; D007378:Interleukins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma