INTERLEUKIN-2-MEDIATED STAT-5 EXPRESSION LEVELS IN CD8+CD25+ REGULATORY T CELLS: THE RELEVANCE FOR ASTHMA

Abstract

Preliminary studies demonstrated the potential role of CD8⁺CD25⁺ T regulatory cells (Tregs) in asthma. However, published data with regard to the relevance of signaling pathways that govern Tregs homeostasis are limited and conflicting. The first aim of this study was to characterize the phosphorylation of STAT-5 in CD8⁺CD25⁺ Tregs. The second aim was to investigate the ability of CD8⁺CD25⁺ Tregs from patients and controls to respond to interleukin (IL)-2 treatment in vitro. Twenty-five healthy subjects (NC) and 50 patients with either severe (SA) or mild-moderate (MA) asthma were enrolled in the study. STAT-5 phosphorylation was detected in purified CD8⁺CD25⁺ Tregs from healthy and asthma subjects, indicating that STAT-5 has a role in their pathobiology. At baseline, asthmas had either significantly lower [(SA=4.5±5% vs NC=26±25%, P<0.001) and (MA=10±7.5% vs NC=26±25%, P<0.001)] or higher [(SA=54±58.5% vs 26±25%, P<0.01) and (MA=71±74.5% vs 26±25%, P<0.01) proportion of Tregs expressing pSTAT-5 than controls. In contrast to healthy subjects, CD8⁺CD25⁺ Tregs from asthma subjects had either increased (pSTAT-5high) or decreased (pSTAT-5low) phosphorylated STAT-5 levels within individual cells. These data suggest that the alteration in STAT5 phosphorylation level might be associated with asthma and is a potential molecular basis of skewed CD8⁺CD25⁺ Treg differentiation. IL-2 treatment of cells from severe asthma subjects increased the proportion of cells expressing high level of pSTAT-5 while it decreased the proportion of those expressing low level of pSTAT-5. Strikingly, IL-2 increased the proportions of both subsets from mild-moderate asthma subjects. These findings demonstrate that altered IL-2-mediated STAT-5 phosphorylation within individual circulatory CD8⁺CD25⁺ Tregs may be associated with asthma and disease severity