Elsevier

Clinical Immunology

Volume 105, Issue 2, November 2002, Pages 126-140
Clinical Immunology

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

https://doi.org/10.1006/clim.2002.5273Get rights and content

Abstract

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.

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    This work was supported by NIH Grants AI24258 and CA49605 to P.P. W.H.C. was supported by the following grants: NIH Training Grant T32 AI07290-13,-14,-15 and the United Negro College Fund–Merck Science Initiative Fellowship and NIH K08 AI50779-01.

    2

    To whom correspondence should be addressed at the Department of Structural Biology, Stanford University, Stanford, CA 94305-5126. Fax: (650) 723-8464. E-mail: [email protected].

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