Gene and protein characteristics reflect functional diversity of CD56dim and CD56bright NK cells

Abstract

Recent findings underline the role of NK cell subsets in regulating adaptive immunity. To define characteristics of NK cell subpopulations, purified CD56(dim) and CD56(bright) NK cells were analyzed by using gene chip arrays covering more than 39,000 transcripts. Gene profiling revealed resting NK cells to differ in respect to 473 transcripts with 176 exclusively expressed in CD56(dim) and 130 solely in CD56(bright) NK cells. Results were compared with array analyses using mRNA obtained from activated CD56(dim) and CD56(bright) NK cells. In this approach, NK cell receptors, cytolytic molecules, adhesion structures, and chemokine ligands showed differential expression patterns in the two subpopulations. These data were validated using FACS, RT-qPCR, or cytokine bead array (CBA) techniques. Cytokines produced by CD56(dim) and CD56(bright) NK cells were determined using a protein array covering 79 different bioactive mediators. GDNF, IGFBP-1, EGF, and TIMP-2 were detected in both subsets. In contrast, IGFBP-3 and IGF-1 were mainly produced by CD56(dim), while GM-CSF, TARC, and TGFbeta3 were expressed by CD56(bright) NK cells. In summary, we report new characteristic features of CD56(dim) and CD56(bright) NK cells, further underscoring that they represent independent populations with functionally diverse capabilities. The information on NK cells generated in this study will help to define corresponding NK cell populations in other species that lack CD56 expression on NK cells, such as mice. This will subsequently lead to the establishment of suitable animal models for detailed analysis of NK cell populations in vivo.

Ex Vivo Generated Natural Killer Cells Acquire Typical Natural Killer Receptors and Display a Cytotoxic Gene Expression Profile Similar to Peripheral Blood Natural Killer Cells

“…Importantly, the gene expression profiling highlighted a potentially mature repertoire of cytotoxic molecules expressed by the ex vivo differentiated NK cells. By more closely examining the expression of perforin and various granzymes by real-time RT-PCR, we were able to show that the ex vivo generated NK cells, similar to CD56 dim PBNK cells, express higher levels of granzyme A, granzyme B, and perforin and lower levels of granzyme K when compared to CD56 bright PBNK cells [38,39]. Therefore, the ex vivo generated NK cells exhibit most important functional prerequisites for strong cytotoxic activity similar to CD56 dim PBNK cells.…”

Herpes Simplex Virus Antigens Directly Activate NK Cells via TLR2, Thus Facilitating Their Presentation to CD4 T Lymphocytes

“…Both MHC II molecules were significantly upregulated on NK cells, and HLA-DR expression was upregulated to the greatest extent on the CD56 bright CD16 2 NK cell subset (data not shown). Expression of MHC II molecules on human NK cells as mRNA and protein was reported (67,68) but not previously shown to be upregulated by lipopeptide or a viral pathogen, although similar lipopeptides induce maturation and upregulate MHC II on DCs (71).…”

“…NK cells can mature DCs and induce the Th1 transcription factor T-bet in CD4 T lymphocytes through IFN-g production (65,66), both of which promote Th1 responses. Hanna et al (28) reported that NK cells (especially the CD56 bright CD16 2 subset) activated by PHA and IL-2 can present Ag, and they defined distinct proteomic and genomic profiles of the two NK cell subsets (67,68).…”

Investigating the potential immune role of fish NCAMs: Molecular cloning and expression analysis in mandarin fish

“…The CD56 bright NK cells represent the main NK cell populations in secondary lymphoid organ and inflamed tissues [49,50]. However, mucosal T cells, whose differentiation and selection are independent of the thymus, can develop much more CD56 þ T cells [52].…”