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Novel Insights on Human NK Cells’ Immunological Modalities Revealed by Gene Expression Profiling

2004; American Association of Immunologists; Volume: 173; Issue: 11 Linguagem: Inglês

10.4049/jimmunol.173.11.6547

1550-6606

Jacob H. Hanna, Pamela E. Bechtel, Yufeng Zhai, Fadi Youssef, Karen R. McLachlan, Ofer Mandelboim,

Reproductive System and Pregnancy

Abstract As part of the innate immune system, human NK cells play a critical role early in the systemic host defense against pathogens and tumor cells. Recent studies suggest a more complex view of NK cell behavior, as different functions and tissue localizing capabilities seem to be preferentially assigned to distinct subpopulations of NK cells, CD56dimCD16+ or CD56brightCD16−. In this study, we used oligonucleotide microarrays to compare the expression profile of ∼20,000 genes in three NK cell subpopulations: peripheral blood-derived CD56dimCD16+, CD56brightCD16−, and in vitro-activated CD16+ NK cells. The differential expression of selected genes was verified by flow cytometry and functional assays. When comparing CD56dimCD16+ and CD56brightCD16− subsets, a new heterogeneous molecular basis for the functional and developmental differences between these two subsets was revealed. Furthermore, systematic analysis of transcriptional changes in activated CD16+ NK cells provided us with a better understanding of NK function in inflamed tissues. We highlight a number of genes that were overexpressed upon activation (e.g., OX40 ligand, CD86, Tim3, galectins, etc.), that enable these cells to directly cross-talk with other innate and adaptive immune effectors. The overexpressed genes assign novel intriguing immunomodulatory functions to activated NK cells, in addition to their potent cytotoxic abilities.