Cell mediated immunity against HPV16 E2, E6 and E7 peptides in women with incident CIN and in constantly HPV-negative women followed-up for 10-years

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.

HPV in Head and Neck Carcinomas: Different HPV Profiles in Oropharyngeal Carcinomas – Why?

“…This might be an indication of a vanished plasticity of Th17 cells in CIN women [101]. The children born to the CIN mothers had also a cytokine profile distinct from that of the children born to HPV-negative mothers [102, 103]. Our recent unpublished data also indicate that TGF-β levels in the sera of the children born to CIN mothers were significantly higher than those found in the control children.…”

Oral manifestations of human papillomavirus infections

“…To conclude, HPV‐16‐specific CMI is common in young, sexually inexperienced children, and oral HPV infections are frequently seen in young children. The T‐helper 2 cell cytokine profile might also predispose to persistent oral HPV‐16 infection in women . We recently showed that the HLA‐G allele concordance might affect the vertical transmission of HPV, especially to the oral cavity .…”

Evaluation of serum interleukin 17 and zinc levels in recalcitrant viral wart

“…However, it remains incompletely understood why there is apparent failure of the immune system in otherwise healthy individuals to clear warts for months or years. Among these individuals, viral warts do not respond to conventional therapies or they recur soon after destructive procedures and persist for months and years …”

“…Among these individuals, viral warts do not respond to conventional therapies or they recur soon after destructive procedures and persist for months and years. 3 Interleukin 17 (IL-17) is a pro-inflammatory cytokine involved in the control of many different disorders that include autoimmune, oncogenic, and many infectious diseases. 4 T cells that produce IL-17 arise as a specific population of CD4-positive T cells, which are called T helper 17 (Th17) cells that are distinct from the classic Th1 and Th2 cells.…”