Expansion of CD4+CD25+ helper T cells without regulatory function in smoking and COPD

Background: Regulatory T cells have been implicated in the pathogenesis of COPD by the increased expression of CD25 on helper T cells along with enhanced intracellular expression of FoxP3 and low/absent CD127 expression on the cell surface. Method: Regulatory T cells were investigated in BALF from nine COPD subjects and compared to fourteen smokers with normal lung function and nine never-smokers. Results: In smokers with normal lung function, the expression of CD25(+)CD4(+) was increased, whereas the proportions of FoxP3(+) and CD127(+) were unchanged compared to never-smokers. Among CD4(+) cells expressing high levels of CD25, the proportion of FoxP3(+) cells was decreased and the percentage of CD127(+) was increased in smokers with normal lung function. CD4(+) CD25(+) cells with low/absent CD127 expression were increased in smokers with normal lung function, but not in COPD, when compared to never smokers. Conclusion: The reduction of FoxP3 expression in BALF from smokers with normal lung function indicates that the increase in CD25 expression is not associated with the expansion of regulatory T cells. Instead, the high CD127 and low FoxP3 expressions implicate a predominantly non-regulatory CD25(+) helper T-cell population in smokers and stable COPD. Therefore, we suggest a smoking-induced expansion of predominantly activated airway helper T cells that seem to persist after COPD development.