Abstract
BackgroundVirus-specific cell-mediated immunity (CMI) plays a role in the outcome of genital HPV infections. To cast further light on the question why most women clear their HPV infection while others develop high-grade cervical intraepithelial neoplasia (CIN), we analyzed HPV16 E2-, E6- and E7 -specific CMI in women who developed CIN during a 10-year follow-up of the Finnish Family HPV cohort.MethodsOverlapping 30–35 mer peptides covering the entire HPV16 E2-, E6- and E7 protein sequences were used for defining the lymphocyte proliferation capacity, cytokine production (IL-2, IL-5, IL-10, IL-17A, IFN-γ and TNF-α) and numbers of HPV16 -specific CD4+ CD25+ Foxp3+ regulatory T-cells in 10 women who developed CIN, and in 22 control women who tested constantly HPV-negative during the follow-up. HPV-specific CMI was related to the demographic data including sexual behavior, smoking and alcohol consumption.ResultsWomen with CIN and their controls had similar T-cell mediated immunity against HPV16 E2, E6 and E7 peptide pools. However, nearly fourfold higher T-cell reactivity against common antigens was found in the CIN women than in the healthy donors (p = 0.001). HPV16 E6 stimulation resulted in higher IL-17A secretion in the controls than in the CIN women (p = 0.035). Smoking and use of alcohol affected the T-cell response to common antigens but not to HPV peptides (p = 0.032 and 0.045, respectively).ConclusionWhile both the CIN women and controls exhibited an HPV16-specific CMI, IL-17A might be of importance in HPV induced pathology. The hyper-responsiveness of the CIN patients to common antigens needs further studies. Smoking and alcohol had no effect on HPV-specific CMI.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0498-9) contains supplementary material, which is available to authorized users.
Highlights
Virus-specific cell-mediated immunity (CMI) plays a role in the outcome of genital human papillomavirus (HPV) infections
The mucosal HPVs are classified as either high(HR) or low-risk (LR) types based on their oncogenic potential [1]
Our results indicate that the high Memory response mix (MRM) response was related indirectly rather to the presence of genital HPV and not oral HPV
Summary
Virus-specific cell-mediated immunity (CMI) plays a role in the outcome of genital HPV infections. To cast further light on the question why most women clear their HPV infection while others develop high-grade cervical intraepithelial neoplasia (CIN), we analyzed HPV16 E2-, E6- and E7 -specific CMI in women who developed CIN during a 10-year follow-up of the Finnish Family HPV cohort. The majority of healthy women without any genital HPV disease mount blood T-cell responses against HPV16 E2, E6 and E7 proteins [12,13]. Given that E2 protein is absent in viral particles but needed in viral replication, E2 T-cell responses might indicate a replicative HPV infection [17]. CMI against E2 protein could be the most likely candidate to reflect differences between the women with and without cervical diseases
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