NK Cell-Mediated Lysis of Autologous HCMV-Infected Skin Fibroblasts Is Highly Variable among NK Cell Clones and Polyclonal NK Cell Lines

Lysis of human cytomegalovirus (HCMV)-infected fibroblasts by autologous natural killer (NK) cells was examined in vitro. For NK cell clones, receptor expression was determined at the level of mRNA and cell-surface protein and compared to the lysis of HCMV AD169 strain-infected fibroblasts in which...

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Veröffentlicht in:Clinical immunology (Orlando, Fla.) Fla.), 2002-11, Vol.105 (2), p.126-140
Hauptverfasser: Carr, William H., Little, Ann-Margaret, Mocarski, Edward, Parham, Peter
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Sprache:eng
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Zusammenfassung:Lysis of human cytomegalovirus (HCMV)-infected fibroblasts by autologous natural killer (NK) cells was examined in vitro. For NK cell clones, receptor expression was determined at the level of mRNA and cell-surface protein and compared to the lysis of HCMV AD169 strain-infected fibroblasts in which HLA class I was >70% downregulated. The clones ranged broadly in their ability to lyse AD169-infected fibroblasts, correlating neither with the expression of inhibitory KIR, leukocyte inhibitory receptor-1, or CD94:NKG2A receptors nor with the number of different inhibitory KIR expressed per clone. Some lines of polyclonal NK cells preferentially lysed AD169-infected cells and similarly lysed fibroblasts infected with mutant virus RV798, which lacks the genes for downregulating HLA class I. These results demonstrate that NK cell lysis of HCMV-infected autologous fibroblasts is more complex than a simple missing-self mechanism involving downregulation of HLA class I and failure to engage inhibitory self-specific KIR.
ISSN:1521-6616
1521-7035
DOI:10.1006/clim.2002.5273