Potential role of interleukin-18 in the immunopathogenesis of AIDS: involvement in fratricidal killing of NK cells.
We had shown earlier that the concentrations of circulating interleukin-18 (IL-18) are increased significantly in human immunodeficiency virus (HIV)-infected persons compared to HIV-seronegative healthy subjects. In the present study, we investigated the consequences of these elevated levels of IL-18 on natural killer (NK) cells and the immunopathogenesis of AIDS. We show here an inverse correlation between IL-18 concentrations and absolute numbers of various subsets of NK cells in infected persons. Recombinant human IL-18 caused increased death of a human NK cell line, as well as of primary human NK cells in vitro. The IL-18-mediated cell death was dependent upon Fas-FasL interactions and tumor necrosis factor alpha. IL-18 induced the expression of FasL on NK cells, increased the transcription from the human FasL promoter, reduced the expression of Bcl-X(L) in NK cells, and increased their sensitivity to FasL-mediated cell death. These results suggest that increased IL-18 concentrations present in the circulation of HIV-infected persons contribute to the immunopathogenesis of AIDS by altering NK cell homeostasis.
Iannello
Alexandre
A
Department of Microbiology and Immunology, Laboratory of Innate Immunity, CHU-Sainte-Justine Research Center, University of Montreal, Montreal, Quebec, Canada.
Samarani
Suzanne
S
Debbeche
Olfa
O
Ahmad
Rasheed
R
Boulassel
Mohamed-Rachid
MR
Tremblay
Cécile
C
Toma
Emil
E
Routy
Jean-Pierre
JP
Ahmad
Ali
A