Natural cell-mediated cytotoxicity of peripheral blood lymphocytes against target cells transfected with epidermodysplasia verruciformis-specific human papillomavirus type 8 L1 DNA sequences.
The aim of the present study was to characterise natural cell-mediated cytotoxicity against COS-7 cells transfected with potentially oncogenic HPV-8 L1 DNA sequences cloned in sense and antisense orientation and to evaluate their lysis by peripheral blood lymphocytes (PBL) from patients with epidermodysplasia verruciformis (EV), a rare disease associated with life-long infection by specific HPV types. COS-7 cells were transfected with HPV-8 Hinc II restriction fragment (nucleotide positions 5434-7654) cloned in sense (COS-L1S) and antisense (COS-L1A) orientation into pCB6 expression vector. Cytotoxic activity of isolated PBL against COS cell lines as well as K562 erythroleukaemic cells was evaluated by 51Cr-release assay. We found that lymphocytes responsible for natural lysis of COS and K562 cells are CD3-negative CD56-positive natural killer (NK) cells. Analysis of NK cell cytotoxic activity against different COS cell lines has revealed that lymphocytes from healthy subjects killed COS-L1S cells significantly more efficiently than wild COS-7 and COS-L1A cells. Significantly more efficient lysis of COS-L1S cells was also observed in EV patients. Thus, expression of HPV L1 renders target cells more susceptible to NK-mediated cytotoxicity that may enable more effective elimination of transformed cells.
Oldak
Monika
M
Department of Histology and Embryology, Center of Biostructure Research, Medical University of Warsaw, PL-02004 Warsaw, Poland. monika.oldak@ib.amwaw.edu.pl
Majewski
Slawomir
S
Grzela
Tomasz
T
Stark
Sabine
S
Malejczyk
Magdalena
M
Osiecka-Iwan
Anna
A
Fuchs
Pawel G
PG
Jablonska
Stefania
S
Pfister
Herbert J
HJ
Malejczyk
Jacek
J
D000328:Adult; D000818:Animals; D019556:COS Cells; D004819:Epidermodysplasia Verruciformis / Q000821:virology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D027383:Papillomaviridae / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D014162:Transfection
D009856:Oncogene Proteins, Viral