OBJECTIVE: Increasing evidence shows that autoimmune response contributes importantly to pathogenesis of abdominal aortic aneurysm (AAA). This work was aimed to assess the possibly altered function of peripheral CD4(+)CD25(+) T regulatory cells (Tregs) that might breakdown immunologic self-tolerance in AAA patients. METHODS AND RESULTS: Peripheral blood from 22 AAA patients, 11 patients with abdominal aortic atherosclerotic occlusive disease (AOD), and 32 healthy controls (HCs) was analyzed to determine the percentage of CD4(+)CD25(+) Tregs in the total CD4(+) T-cell population and FOXP3 expression by means of flow cytometry. The frequencies of the CD4(+)CD25(+) Treg population were not significantly different between groups (AAA, 5.69+/-0.99%; AOD, 5.52+/-1.13%; HC, 5.88+/-1.55%; P>0.05). However, the frequency of CD4(+)CD25(+)FOXP3(+) T cells in AAA patients (2.45+/-0.57%) was significantly lower than that in AOD group (3.41+/-0.72%; P<0.01) or in HCs (3.69+/-0.82%; P<0.01). A comparison of FOXP3 mRNA and protein expression revealed significantly lower levels in CD4(+)CD25(+) Tregs from AAA group than either of other 2 groups (P<0.01). Suppressive function assay showed that freshly isolated CD4(+)CD25(+) Tregs from patients with AAA exhibited significantly less suppressive activity than those from AOD patients or HCs (P<0.01). Mixing cultures with CD4(+)CD25(+) T cells and CD4(+)CD25(-) T cells from AAA patients and HCs demonstrated that the primary regulatory defect is due to a dysfunction of CD4(+)CD25(+) Tregs, and not a resistance of CD4(+)CD25(-) responder T cells to suppression in AAA patients. CONCLUSIONS: Our data demonstrate a reduced level of FOXP3 expression in peripheral CD4(+)CD25(+) Tregs and decreased frequency of CD4(+)CD25(+)FOXP3(+) T cells in a cohort of AAA patients enrolled in the study, which leads to a functional deficiency of CD4(+)CD25(+) Tregs as a whole. This indicates an impaired immunoregulation by Tregs that may contribute to AAA pathogenesis.
OBJECTIVE: Increasing evidence shows that autoimmune response contributes importantly to pathogenesis of abdominal aortic aneurysm (AAA). This work was aimed to assess the possibly altered function of peripheral CD4(+)CD25(+) T regulatory cells (Tregs) that might breakdown immunologic self-tolerance in AAA patients. METHODS AND RESULTS: Peripheral blood from 22 AAA patients, 11 patients with abdominal aortic atherosclerotic occlusive disease (AOD), and 32 healthy controls (HCs) was analyzed to determine the percentage of CD4(+)CD25(+) Tregs in the total CD4(+) T-cell population and FOXP3 expression by means of flow cytometry. The frequencies of the CD4(+)CD25(+) Treg population were not significantly different between groups (AAA, 5.69+/-0.99%; AOD, 5.52+/-1.13%; HC, 5.88+/-1.55%; P>0.05). However, the frequency of CD4(+)CD25(+)FOXP3(+) T cells in AAA patients (2.45+/-0.57%) was significantly lower than that in AOD group (3.41+/-0.72%; P<0.01) or in HCs (3.69+/-0.82%; P<0.01). A comparison of FOXP3 mRNA and protein expression revealed significantly lower levels in CD4(+)CD25(+) Tregs from AAA group than either of other 2 groups (P<0.01). Suppressive function assay showed that freshly isolated CD4(+)CD25(+) Tregs from patients with AAA exhibited significantly less suppressive activity than those from AOD patients or HCs (P<0.01). Mixing cultures with CD4(+)CD25(+) T cells and CD4(+)CD25(-) T cells from AAA patients and HCs demonstrated that the primary regulatory defect is due to a dysfunction of CD4(+)CD25(+) Tregs, and not a resistance of CD4(+)CD25(-) responder T cells to suppression in AAA patients. CONCLUSIONS: Our data demonstrate a reduced level of FOXP3 expression in peripheral CD4(+)CD25(+) Tregs and decreased frequency of CD4(+)CD25(+)FOXP3(+) T cells in a cohort of AAA patients enrolled in the study, which leads to a functional deficiency of CD4(+)CD25(+) Tregs as a whole. This indicates an impaired immunoregulation by Tregs that may contribute to AAA pathogenesis.
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