Increased expression of programmed death (PD)-1 and its ligand PD-L1 correlates with impaired cell-mediated immunity in high-risk human papillomavirus-related cervical intraepithelial neoplasia

Autor:	Yan Song, Jun-Zhong Sun, Wen Yang, Yun-Long Lu, Hong-Wei Wang
Rok vydání:	2013
Předmět:	Adult Cellular immunity Biopsy T-Lymphocytes medicine.medical_treatment Programmed Cell Death 1 Receptor Immunology Uterine Cervical Neoplasms Enzyme-Linked Immunosorbent Assay Biology Cervical intraepithelial neoplasia B7-H1 Antigen Human Papillomavirus DNA Tests Interferon-gamma Immunity PD-L1 medicine Humans Immunology and Allergy Papillomaviridae Neoplasm Staging CD86 Immunity Cellular Papillomavirus Infections virus diseases Original Articles Dendritic Cells Exudates and Transudates Immunotherapy Flow Cytometry Uterine Cervical Dysplasia medicine.disease Interleukin-12 female genital diseases and pregnancy complications Interleukin-10 Up-Regulation Cytokine Case-Control Studies B7-1 Antigen biology.protein Female B7-2 Antigen CD80
Zdroj:	Immunology. 139:513-522
ISSN:	0019-2805
DOI:	10.1111/imm.12101
Popis:	Impaired local cellular immunity contributes to the pathogenesis of persistent high-risk human papillomavirus (HR-HPV) infection and related cervical intraepithelial neoplasia (CIN), but the underlying molecular mechanisms remain unclear. Recently, the programmed death 1/programmed death 1 ligand (PD-1/PD-L1; CD279/CD274) pathway was demonstrated to play a critical role in attenuating T-cell responses and promoting T-cell tolerance during chronic viral infections. In this study, we examined the expression of PD-1 and PD-L1 on cervical T cells and dendritic cells (DCs), respectively, from 40 women who were HR-HPV-negative (−) or HR-HPV-positive (+) with CIN grades 0, I and II–III. We also measured interferon-γ, interleukin-12 (IL-12) and IL-10 in cervical exudates. The most common HPV type was HPV 16, followed by HPV 18, 33, 51 and 58. PD-1 and PD-L1 expression on cervical T cells and DCs, respectively, was associated with HR-HPV positivity and increased in parallel with increasing CIN grade. The opposite pattern was observed for CD80 and CD86 expression on DCs, which decreased in HR-HPV(+) patients in parallel with increasing CIN grade. Similarly, reduced levels of the T helper type 1 cytokines interferon-γ and IL-12 and increased levels of the T helper type 2 cytokine IL-10 in cervical exudates correlated with HR-HPV positivity and CIN grade. Our results suggest that up-regulation of the inhibitory PD-1/PD-L1 pathway may negatively regulate cervical cell-mediated immunity to HPV and contribute to the progression of HR-HPV-related CIN. These results may aid in the development of PD-1/PD-L1 pathway-based strategies for immunotherapy of HR-HPV-related CIN.
Databáze:	OpenAIRE
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