title: Patients with Wegener's granulomatosis demonstrate a relative deficiency and functional impairment of T-regulatory cells.
abstract: An increased proportion of CD4(+) CD25(+) T cells has been reported in Wegener's granulomatosis (WG) and may represent an accumulation of regulatory T cells (Treg). CD25 is also expressed on recently activated effector T cells. We have determined the relative proportion of these subsets in a large patient cohort. The fraction of Treg in peripheral blood mononuclear cells from patients and healthy controls was determined by assessment of Foxp3 expression on CD4(+) CD25(+) T cells. The functional activity of Treg was determined by their ability to suppress proliferation and cytokine production in response to proteinase-3. Although WG patients demonstrated an increased fraction of CD4(+) CD25(+) T cells, the percentage of Foxp3-positive cells was decreased. In addition, the percentage of Treg was inversely related to the rate of disease relapse. CD4(+) CD25(hi) T cells were able to suppress T-cell proliferation to proteinase-3 in healthy controls and anti-neutrophil cytoplasm antibody (ANCA)- negative patients (at time of sampling) but not in ANCA-positive patients. In patients with active disease, an increased proportion of CD4(+) Foxp3(+) cells was associated with a more rapid disease remission. Patients with WG demonstrate abnormalities in the number and function of Treg and this is most pronounced in those with most active disease. This information is of value in understanding the pathogenesis and potential treatment of this disease.
authors.affiliation: Renal Immunobiology, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Morgan
authors.forename: Clara J
authors.initials: CJ
authors.lastname: Day
authors.forename: Karen P
authors.initials: KP
authors.lastname: Piper
authors.forename: Naeem
authors.initials: N
authors.lastname: Khan
authors.forename: Lorraine
authors.initials: L
authors.lastname: Harper
authors.forename: Paul A
authors.initials: PA
authors.lastname: Moss
authors.forename: Caroline O S
authors.initials: CO
authors.lastname: Savage
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood / Q000276:immunology; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology; D014890:Granulomatosis with Polyangiitis / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors