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Patients with Wegener’s granulomatosis demonstrate a relative deficiency and functional impairment of T‐regulatory cells
Author(s) -
Morgan Matthew D.,
Day Clara J.,
Piper Karen P.,
Khan Naeem,
Harper Lorraine,
Moss Paul A.,
Savage Caroline O. S.
Publication year - 2010
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2009.03213.x
Subject(s) - foxp3 , il 2 receptor , immunology , flow cytometry , pathogenesis , cytokine , effector , regulatory t cell , medicine , peripheral blood mononuclear cell , biology , t cell , in vitro , immune system , biochemistry
Summary 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.