A subpopulation of human peripheral blood NK cells that lacks inhibitory receptors for self-MHC is developmentally immature.
How receptor acquisition correlates with the functional maturation of natural killer (NK) cells is poorly understood. We used quantitative real-time polymerase chain reaction (PCR) assays to compare NKG2 and killer immunoglobulin-like receptor (KIR) gene expression in NK cells from allogeneic transplant recipients and their donors. Marked differences were observed in the NK subsets of recipients who had 8-fold more CD56(bright) cells, diminished KIR expression (except 2DL4), and increased NKG2A. In normal blood not all CD56(dim) cells express KIR, and a novel subpopulation of cells committed to the NK-cell lineage was defined. These cells, which comprise 19.4% +/- 2.8% of the CD56(dim) NK population in healthy donors, express the activating NKG2D and NKG2E receptors but no KIR or NKG2A. Although the CD56(dim) NKG2A(-) KIR(-) NK cells lack "at least one" inhibitory receptor for autologous MHC class I, they are not fully responsive, but rather functionally immature cells with poor cytotoxicity and IFN-gamma production. Upon culture with IL-15 and a stromal cell line, CD56(dim) and CD56(bright) KIR(-) NK cells proliferate, express KIR, and develop cytotoxicity and cytokine-producing potential. These findings have implications for the function of NK cells reconstituting after transplantation and support a model for in vivo development in which CD56(bright) cells precede CD56(dim) cells.
Cooley
Sarah
S
Division of Hematology, Oncology and Transplantation, University of Minnesota Cancer Center, Minneapolis 55455, USA.
Xiao
Feng
F
Pitt
Michelle
M
Gleason
Michelle
M
McCullar
Valarie
V
Bergemann
Tracy L
TL
McQueen
Karina L
KL
Guethlein
Lisbeth A
LA
Parham
Peter
P
Miller
Jeffrey S
JS
D019002:CD56 Antigen / Q000276:immunology; D018929:Cell Culture Techniques; D017931:DNA Primers; D004532:Ego; D005434:Flow Cytometry; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000235:genetics*; D055654:NK Cell Lectin-Like Receptor Subfamily C; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics; D055607:Receptors, Natural Killer Cell; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017634:Self Tolerance
D019002:CD56 Antigen; D017931:DNA Primers; C527054:KLRC1 protein, human; C527062:KLRC3 protein, human; C527085:KLRK1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D007371:Interferon-gamma