Upregulation of FOXP3+Regulatory T Lymphocytes and CD8+Lymphocytes in Patients with High-Grade Squamous Intraepithelial Lesions Correlated with HPV Infection

Abstract

Modern therapeutic strategies for precancerous cervical intraepithelial neoplasia (CIN) focus on immune-modulatory and cancer vaccination. The local cervical immune status in cervical cancer and CIN could influence HPV infection persistence, progression and carcinogenesis. We analysed the role of FOXP3+ regulatory T lymphocytes, CD4+ and CD8+ T lymphocytes in CIN I, CIN II and CIN III patients with and without HPV infection. Sixty-two patients were enrolled in the study. Each patient underwent a colposcopy-guided cervical biopsy. FOXP3+ lymphocytes and CD4+,CD8+ lymphocytes were detected by immunostaining in tissue samples obtained from a control group (n = 10), patients with CIN I (n = 20), CIN II (n = 14) and CIN III (n = 18) lesions. HPV was assayed by Aptima. The results showed that the numbers of CD4+ T lymphocytes did not differ between patients with CIN I, CIN II, and CIN III. However, patients with CIN II and CIN III had significantly upregulated CD8+T lymphocytes compared to patients with CIN I. In addition, patients with CIN II and CIN III had increased FOXP3 + T lymphocytes compared with patients with CIN I, which was associated with HPV status. Upregulation of FOXP3+ regulatory T lymphocytes and CD8-positive lymphocytes in patients with CIN II and CIN III suggested a pivotal role of T regulatory lymphocytes and CD8+ lymphocytes for counteracting the host immune response in the progression from CIN I to CIN II and CIN III.