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.
Design and 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.