Adjuvant BCG immunotherapy induces an effective antiviral immune response in recurrent respiratory papillomatosis

Recurrent respiratory papillomatosis (RRP) caused by human papillomavirus (HPV) is characterized by proliferation of premalignant squamous papillomas within the respiratory tract. The disease has often dramatic presentation due to significant airway obstruction, high relapse frequency and unpredictable prognosis as a result of inefficient immune response to chronic HPV infection. The adjuvant BCG immunotherapy considerably improves the outcome. The present study investigates the effects of BCG on the antiviral immune response of RRP patients. RRP patients (n = 17) subjected to combined CO 2 laser microsurgery / BCG-immunotherapy were studied before (0), 6, 12 and 20 months after the start of immunomodulation. The percentages of effector and regulatory T lymphocytes, as well as Th1/Th2 cytokine secretion were determined by flow cytometry, in comparison to healthy controls. Initially increased levels of IFNg-secreting CD4 (Th1) and CD8 (Tc1) cells in untreated RRP patients were normalized to healthy control levels after 20 months of BCG immunotherapy. Further on, 12 months of BCG immunotherapy significantly decreased the share of proinflammatory Th17 (0.4 vs. 0.69, p BCG immunotherapy increases the efficiency of antiviral T-cell response by restoring Th1/Th2/Th17 cytokine balance and inducing the differentiation of Treg preventing the terminal differentiation of T cell clones in the settings of chronic infection.