PHENOTYPIC CHARACTERIZATION OF EX VIVO CD4+CD25HIGHCD127LOW IMMUNE REGULATORY T CELLS IN ALLERGIC ASTHMA: PATHOGENESIS RELEVANCE OF THEIR FOXP3, GITR, CTLA-4 AND FAS EXPRESSIONS

Background: CD4(+)CD25(high) regulatory T (Treg) cells are crucial for immune homeostasis and peripheral tolerance, but their relevance to allergic asthma has not been fully elucidated. Objective: To assess peripheral blood CD4(+) T cells, and CD4(+)CD25(high)CD127(low) Treg cells expressing phenotypic markers (FoxP3, GITR, CTLA-4, and FAS) in allergic asthma subjects. Materials and Methods: Peripheral blood mononuclear cells were isolated from 60 allergic asthma (AA) subjects and 30 healthy controls (HC). We examined by flow cytometry, the proportion of CD4(+) T cells and CD4(+)CD25(high)CD127(low) Treg cells as well as the expression of FoxP3, GITR, CTLA-4, and FAS by CD4(+)CD25(high)CD127(low) Treg cells. Moreover, FOXP3 mRNA expression was measured by quantitative real time polymerase chain reaction (real-time RT-PCR). Results: The absolute number of CD4(+)CD25(high)CD127(low) Treg cells and the percentages of CD4(+)CD25(high)CD127(low) Treg cells expressing one of the four selected markers were significantly lower in allergic asthma subjects compared with controls. We observed no significant decreased absolute CD4(+) T cell count in the examined groups compared to the control group. Except for GITR, circulatory CD4(+)CD25(high)CD127(low) Treg cells of severe allergic asthma (SA) subjects showed significantly lower expressions of FoxP3, CTLA-4, and CD95 than did those isolated from mild to moderate asthma (MA) patients. There was no statistically significant difference in the level of mRNA FoxP3 expression in CD4(+)CD25(+) Treg cells between allergic asthma subjects and healthy controls groups, and within the examined groups (p>0.05). Conclusions: These findings suggest that allergic asthma and the use of glucocorticosteroids are associated with decreased absolute number of circulatory CD4(+)CD25(high)CD127(low) Treg cells and the decreased frequencies of CD4(+)CD25(high)CD127(low) Treg cells expressing one of the four selected markers.