Comparison of cervical and blood T-cell responses to human papillomavirus-16 in women with human papillomavirus-associated cervical intraepithelial neoplasia.
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-gamma (IFN-gamma) production was HPV type-specific. Comparing HPV-specific T-cell IFN-gamma 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-gamma 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-gamma 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.
Passmore
Jo-Ann S
JA
Division of Medical Virology, Department Clinical Laboratory Science and Institute of Infectious Disease and Molecular Medicine, Cape Town, South Africa. joann@curie.uct.ac
Milner
Michelle
M
Denny
Lynnette
L
Sampson
Candice
C
Marais
Dianne J
DJ
Allan
Bruce
B
Gumbi
Pam P
PP
Hitzeroth
Inga I
II
Rybicki
Edward P
EP
Williamson
Anna-Lise
AL
D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D002584:Cervix Uteri / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D039841:Leukocyte L1 Antigen Complex / Q000276:immunology; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000276:immunology* / Q000821:virology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D007074:Immunoglobulin G; D039841:Leukocyte L1 Antigen Complex; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma