Defective killing activity against gp120/41-expressing human erythroleukaemic K562 cell line by monocytes and natural killer cells from HIV-infected individuals.
OBJECTIVE
To determine the role of natural cellular cytotoxicity of peripheral blood mononuclear cells (PBMC) in killing of HIV-1 envelope protein-expressing, natural killer (NK)-sensitive human target cells, and to investigate this effector function in HIV-infected individuals.


METHODS
An HIV-1 env gene-containing expression vector was transfected into NK-sensitive K562 cells, and cell clones expressing gp120/41 were selected and used as targets in natural cytotoxicity assays using PBMC from both HIV-seropositive and seronegative individuals. A 16h 51Cr-release assay was used to determine the susceptibility of the gp120/41-expressing K562 as well as control vector-transfected cells. To identify the cell types involved in the killing of the transfected cells, PBMC depleted for a specific cell type as well as enriched or purified cell types were used as effector cells.


RESULTS
Endogenous expression of gp120/41 by target cells increased their susceptibility to lysis by PBMC of HIV-seronegative individuals. The two cell types responsible for this enhanced killing, NK cells and monocytes, were found severely compromised in HIV-seropositive individuals in their ability to kill both env gene-transfected and control cells; killing by monocytes occurred via CD4.


CONCLUSIONS
The present results illustrate for the first time that the transfected gp120/41 serves as target for both NK and monocyte-mediated killing and that cytocidal activity of these two effector cell types is defective in HIV-infected subjects. Strengthening this innate cytotoxic activity in these individuals may represent a valuable approach in controlling HIV infection.
Ahmad
A
A
Department of Microbiology and Immunology, University of Montreal/Ste-Justine Hospital, Quebec, Canada.
Menezes
J
J
D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002459:Cell Fusion / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D015752:Genes, env / Q000235:genetics; D015699:HIV Envelope Protein gp120 / Q000096:biosynthesis / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000096:biosynthesis / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D004915:Leukemia, Erythroblastic, Acute; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016131:Lymphocyte Subsets; D009000:Monocytes / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41