Reference : Organotypic Culture of HPV-Transformed Keratinocytes: A Model for Testing Lymphocyte ...
Scientific journals : Article
Human health sciences : Immunology & infectious disease
Human health sciences : Oncology
http://hdl.handle.net/2268/19052
Organotypic Culture of HPV-Transformed Keratinocytes: A Model for Testing Lymphocyte Infiltration of (Pre)Neoplastic Lesions of the Uterine Cervix
English
Jacobs, Nathalie mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
Moutschen, Michel P mailto [Université de Liège - ULg > > > > > >]
Franzen-Detrooz, E. [> > > >]
Boniver, V. [> > > >]
Boniver, Jacques mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques]
Delvenne, Philippe mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
Apr-1998
Virchows Archiv : An International Journal of Pathology
432
4
323-30
Yes (verified by ORBi)
International
0945-6317
[en] Organotypic culture ; Human papillomavirus ; Lymphocytes ; uterine cervix ; anti-CD3
[en] The aim of our study was to establish the relevance of an in vitro model for analysing the ability of human lymphocytes to infiltrate human papillomavirus (HPV)-associated (pre)neoplastic lesions of the uterine cervix. To mimic these lesions, we have used the organotypic raft culture of HPV-transformed keratinocytes (SiHa). The SiHa organotypic raft culture was co-cultured with resting or prestimulated (IL-2 or IL-2+anti-CD3 mAb) allogeneic peripheral blood mononuclear cells (PBMC) for 24 and 72 h. The majority of infiltrating cells were T lymphocytes. Occasional NK cells were also identified. The stimulation with IL-2+anti-CD3 mAb induced the highest number of infiltrating cells, with the maximum lymphocyte infiltration observed after 24 h of co-culture. The lymphocyte infiltration was associated with an increased number of apoptotic cells in the organotypic cultures. The ability of PBMC and purified T cell and NK cell populations to lyse HPV-transformed keratinocytes was also investigated on monolayer cultures. As expected in an allogenic model, the highest cytotoxicity was mediated by NK cells activated by IL-2 or IL-2+anti-CD3 mAb. The cytotoxic activity of T cells was weak but, interestingly, increased in the presence of phytohaemagglutinin A (PHA), assuming that T cells were able to kill HPV-infected keratinocytes when a bridge between T cells and keratinocytes was provided. In conclusion, the organotypic culture of HPV-transformed keratinocytes may provide an effective in vitro model for investigating novel T cell-based immunotherapy protocols for the treatment of HPV-associated lesions.
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS ; Centre de Recherche Interuniversitaire en Vaccinologie (région Wallonne et GSK) ; Centre anticancéreux près l′Université de Liège
Researchers ; Students
http://hdl.handle.net/2268/19052

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