Conjugation of HPV16 E7 to cholera toxin enhances the HPV-specific T-cell recall responses to pulsed dendritic cells in vitro in women with cervical dysplasia.
We have evaluated whether cholera toxin (CT) as a carrier/adjuvant can enhance human T-cell responses to a viral oncoprotein in vitro using dendritic cells (DCs) as antigen-presenting cells. Monocyte-derived DCs obtained from women with cervical dysplasia were pulsed with the HPV16 oncoprotein E7, either alone or conjugated to CT, and tested for their ability to induce antigen-specific activation of autologous T cells in vitro. CT-conjugation of E7 significantly improved the capacity of pulsed DCs to activate antigen-specific CD4+ T-cell proliferation and IFN-gamma secretion. The CT-E7-pulsed DCs also produced significantly more of the Th1-inducing cytokine IL-12 compared to DCs pulsed with E7 or CT alone. Furthermore, DCs pulsed with CT-conjugated HPV16 E7 caused a response in T cells from women with advanced disease (CIN III) as well as in T cells from women that were currently not infected with HPV16. These data show the potential of using CT-conjugated viral oncoproteins for DC-induced T-cell activation in humans.
Nurkkala
Merja
M
Department of Rheumatology & Inflammation Research, University of Gothenburg, Göteborg, Sweden. merja.nurkkala@microbio.gu.se
Wassén
Lotta
L
Nordström
Inger
I
Gustavsson
Inger
I
Slavica
Lucija
L
Josefsson
Agnetha
A
Eriksson
Kristina
K
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002772:Cholera Toxin / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D008213:Lymphocyte Activation; D008875:Middle Aged; D050725:Papillomavirus E7 Proteins / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D018074:Vaccines, Conjugate / Q000276:immunology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000276:immunology*
D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D011994:Recombinant Proteins; D018074:Vaccines, Conjugate; C059731:oncogene protein E7, Human papillomavirus type 16; D018664:Interleukin-12; D007371:Interferon-gamma; D002772:Cholera Toxin