Comparison of cervical and blood T-cell responses to human papillomavirus-16 in women with human papillomavirus-associated cervical intraepithelial neoplasia

Passmore, J. A. S., Milner, M., Denny, L., Sampson, C., Marais, D. J., Allan, B., Gumbi, P. P., Hitzeroth, I. I., Rybicki, E. P., & Williamson, A. L. (2006) Comparison of cervical and blood T-cell responses to human papillomavirus-16 in women with human papillomavirus-associated cervical intraepithelial neoplasia. Immunology, 119(4), pp. 507-514.

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Human papillomaviruses (HPVs) are obligate epithelial pathogens and typically cause localized mucosal infections. We therefore hypothesized that T-cell responses to HPV antigens would be greater at sites of pathology than in the blood. Focusing on HPV-16 because of its association with cervical cancer, the magnitude of HPV-specific T-cell responses at the cervix was compared with those in the peripheral blood by intracellular cytokine staining following direct ex vivo stimulation with both virus-like particles assembled from the major capsid protein L1, and the major HPV oncoprotein, E7. We show that both CD4 + and CD8 + T cells from the cervix responded to the HPV-16 antigens and that interferon-γ (IFN-γ) production was HPV type-specific. Comparing HPV-specific T-cell IFN-γ responses at the cervix with those in the blood, we found that while CD4 + and CD8 + T-cell responses to L1 were significantly correlated between compartments (P = 0.02 and P = 0.05, respectively), IFN-γ responses in both T-cell subsets were significantly greater in magnitude at the cervix than in peripheral blood (P = 0.02 and P = 0.003, respectively). In contrast, both CD4 + and CD8 + T-cell IFN-γ responses to E7 were of similar magnitude in both compartments and CD8 + responses were significantly correlated between these distinct immunological compartments (P = 0.04). We therefore show that inflammatory T-cell responses against L1 (but not E7) demonstrate clear compartmental bias and the magnitude of these responses do reflect local viral replication but that correlation of HPV-specific responses between compartments indicates their linkage.

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22 citations in Scopus
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24 citations in Web of Science®

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ID Code: 54950
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By (since 1996): 15
Export Date: 12 November 2012
Source: Scopus
Keywords: Cervical, Human papillomavirus, Mucosal, T-cell immunity
DOI: 10.1111/j.1365-2567.2006.02465.x
Deposited On: 20 Nov 2012 02:46
Last Modified: 29 May 2013 16:53

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