RGD Reference Report - 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. - Rat Genome Database

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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.

Authors: Yang, Wen  Song, Yan  Lu, Yun-Long  Sun, Jun-Zhong  Wang, Hong-Wei 
Citation: Yang W, etal., Immunology. 2013 Aug;139(4):513-22. doi: 10.1111/imm.12101.
RGD ID: 40822817
Pubmed: (View Article at PubMed) PMID:23521696
DOI: Full-text: DOI:10.1111/imm.12101

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.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Cd274  (CD274 molecule)
Pdcd1  (programmed cell death 1)

Genes (Mus musculus)
Cd274  (CD274 antigen)
Pdcd1  (programmed cell death 1)

Genes (Homo sapiens)
CD274  (CD274 molecule)
PDCD1  (programmed cell death 1)


Additional Information