Superantigen-mediated cellular cytotoxicity is dependent on antigen expression, but independent of the P-glycoprotein multidrug resistance phenotype.
Superantigen-activated T cells can be targeted by monoclonal antibodies (mAb) to lyse MHC class II negative tumour cells. In this study we determined the susceptibility of the T-lymphoblastoid leukaemic cell line CCRF-CEM and its multidrug resistant sublines CCRF VCR100, CCRF VCR1000 and CCRF ADR5000 to lysis by monoclonal antibody-targeted and superantigen-activated T cells (superantigen-dependent cellular cytotoxicity, SDCC). A recombinant fusion protein of protein A and the superantigen Staphylococcus enterotoxin A (SEA) was used together with the mAbs anti-CD7, anti-CD38, anti-CD45RA and 4E3 (anti-P-glycoprotein) to correlate susceptibility to SDCC with expression of the MDR1-gene product. Our results demonstrated SDCC to be independent of MDR1-gene expression. This was further confirmed by blocking the function of Pgp in the leukaemic cell lines with a cyclosporine A derivative, which had no influence on SDCC. As expected, expression of the respective cell surface antigens on target cells had a strong impact on SDCC, although other factors seem to influence efficiency of SDCC as well.
Zehrer
C
C
Department of Oncology/Haematology, Children's University Hospital, Tübingen, Germany.
Beck
J
J
Gekeler
V
V
Ihle
J
J
Holzer
U
U
Dohlsten
M
M
Kalland
T
T
Niethammer
D
D
Dannecker
G E
GE
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000276:immunology; D018432:Drug Resistance, Multiple / Q000235:genetics* / Q000276:immunology; D019008:Drug Resistance, Neoplasm / Q000235:genetics* / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology*; D006801:Humans; D015448:Leukemia, B-Cell / Q000276:immunology*; D015458:Leukemia, T-Cell / Q000276:immunology*; D010641:Phenotype; D018089:Superantigens / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D004768:Enterotoxins; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal