Novel insights on human NK cells' immunological modalities revealed by gene expression profiling.
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, CD56(dim)CD16(+) or CD56(bright)CD16(-). In this study, we used oligonucleotide microarrays to compare the expression profile of approximately 20,000 genes in three NK cell subpopulations: peripheral blood-derived CD56(dim)CD16(+), CD56(bright)CD16(-), and in vitro-activated CD16(+) NK cells. The differential expression of selected genes was verified by flow cytometry and functional assays. When comparing CD56(dim)CD16(+) and CD56(bright)CD16(-) 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.
Hanna
Jacob
J
The Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Bechtel
Pamela
P
Zhai
Yufeng
Y
Youssef
Fadi
F
McLachlan
Karen
K
Mandelboim
Ofer
O
D019002:CD56 Antigen / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000096:biosynthesis / Q000235:genetics; D016130:Immunophenotyping; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017452:Receptors, IgG / Q000096:biosynthesis; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic
D019002:CD56 Antigen; D015815:Cell Adhesion Molecules; D018925:Chemokines; D007155:Immunologic Factors; D017452:Receptors, IgG