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Comparison of cervical and blood T‐cell responses to human papillomavirus‐16 in women with human papillomavirus‐associated cervical intraepithelial neoplasia
Author(s) -
Passmore JoAnn S.,
Milner Michelle,
Denny Lynnette,
Sampson Candice,
Marais Dianne J.,
Allan Bruce,
Gumbi Pam P.,
Hitzeroth Inga I.,
Rybicki Edward P.,
Williamson AnnaLise
Publication year - 2006
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2006.02465.x
Subject(s) - cd8 , cervix , cervical intraepithelial neoplasia , biology , t cell , interferon gamma , immunology , antigen , cervical cancer , cytokine , immune system , cancer , genetics
Summary 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.