HIV-1 gp120/160 expressing transfected cell clones to evaluate the antibody-dependent cellular cytotoxicity (ADCC) during the course of HIV-1 infection.
Transfection by electroporation of the CEM.NKR cell line with a plasmid containing the HIVNL43 gp160 gene resulted in the establishment of HIV-1 gp120/160 expressing CEM.NKR cell clones. The cell-surface expression of the recombinant viral envelope is stable and does not lead to syncytium formation among a substantial number of cells expressing envelope glycoprotein, suggesting that these cells are suitable as targets to monitor HIV-specific ADCC activities with the stage or the progression of HIV-1 disease. By using these cells, the ability of sera from HIV-1 seropositive individuals to mediate ADCC against HIV-1 gp120/160 transfected cells in an antigen-specific manner was established. Approximately 63% of the HIV-infected individuals representing all stages of infection have virus-specific ADCC antibodies. Moreover, sera from healthy seropositive (CDC class II) subjects mediated substantially higher levels of ADCC activity (25.7 +/- 11.5%) than did sera from individuals in CDC class III (10.3 +/- 8.9%) or IVC1 (6.4 +/- 8.1%). The mean ADCC activity for the sera from the seronegative volunteers was 2 +/- 1.3%. The correlation between the ADCC level and CD4 cell depletion remains uncertain. Therefore, the established transfected cell line may be used to probe the role of gp120/160-specific ADCC activity in the development of AIDS and may also prove useful in screening human and murine monoclonal antibodies with potential ADCC activity. Such monoclonals may be useful for future immunotherapeutic agents in conjunction with antiviral chemotherapy.
Virology Research Center, Institut Armand-Frappier, Laval, Quebec, Canada.
A
A
Merzouki
P
P
Patel
S
S
Cassol
M
M
O'Shaughnessy
J
J
Gill
M
M
Arella
D000920:Antibody-Dependent Cell Cytotoxicity; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D015686:Gene Products, env / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D019302:HIV Envelope Protein gp160; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D018023:HIV Seronegativity / Q000276:immunology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007938:Leukemia; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012720:Severity of Illness Index; D014162:Transfection; D014407:Tumor Cells, Cultured
D015686:Gene Products, env; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D011993:Recombinant Fusion Proteins