Role of FOXP3+ CD4+ and FOXP3+ CD8+ T Regulatory Cells in Obstructive Sleep Apnea

Abstract

Objectives:

1) Examine the immune responses which may underlie adenotonsillar hypertrophy (ATH) associated with obstructive sleep apnea (OSA). 2) Discuss the role of effector and regulatory T-cells in the inflammatory process within the tonsil and its association with apnea-hypopnea index (AHI).

Methods:

Prospective tonsil specimens were collected from patients undergoing tonsillectomy for OSA at a tertiary-care pediatric hospital between October 2012 and January 2013. Single cell suspensions of the tonsil samples were stained with fluor-conjugated antibodies against CD3, CD4, CD8, FoxP3 (a regulatory T-cell marker), and CD45RO (an activated effector T-cell marker). The stained cells were then analyzed by flow cytometry. The levels of effector and regulatory T-cells were then correlated with severity of disease, as quantified by AHI determined from polysomnography.

Results:

CD4 effector T-cells (CD4 T-eff) were significantly upregulated in pediatric patients with an AHI 5 relative to those with AHI < 5. This result, calculated by Mann-Whitney two-tailed test, indicates that the fraction of activated T-cells increased with elevated AHI (P < 0.0095). FoxP3+ CD8 T-cells (CD8 TcReg) were present at lower levels in patients with an elevated AHI. When these data were plotted as the ratio of CD8 T-eff to CD8 TcReg versus AHI, a correlation coefficient of 0.67 was observed.

Conclusions:

The significant upregulation of CD4 T-eff and the increased ratio of CD8 T-eff to CD8 TcReg in relation to elevated AHI both suggest a immunologically-driven response that is contributing to ATH and the development of OSA.