Early expression of triggering receptors and regulatory role of 2B4 in human natural killer cell precursors undergoing in vitro differentiation.
In this study we analyzed the progression of cell surface receptor expression during the in vitro-induced human natural killer (NK) cell maturation from CD34(+) Lin(-) cell precursors. NKp46 and NKp30, two major triggering receptors that play a central role in natural cytotoxicity, were expressed before the HLA class I-specific inhibitory receptors. Moreover, their appearance at the cell surface correlated with the acquisition of cytolytic activity by developing NK cells. Although the early expression of triggering receptors may provide activating signals required for inducing further cell differentiation, it may also affect the self-tolerance of developing NK cells. Our data show that a fail-safe mechanism preventing killing of normal autologous cells may be provided by the 2B4 surface molecule, which, at early stages of NK cell differentiation, functions as an inhibitory rather than as an activating receptor.
Sivori
Simona
S
Dipartimento di Medicina Sperimentale, Università di Genova, Via L.B. Alberti 2, 16132 Genoa, Italy.
Falco
Michela
M
Marcenaro
Emanuela
E
Parolini
Silvia
S
Biassoni
Roberto
R
Bottino
Cristina
C
Moretta
Lorenzo
L
Moretta
Alessandro
A
D015703:Antigens, CD; D024201:Bystander Effect; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007694:Killer Cells, Natural / Q000276:immunology / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D055627:Natural Cytotoxicity Triggering Receptor 1; D055628:Natural Cytotoxicity Triggering Receptor 3; D011971:Receptors, Immunologic / Q000502:physiology*; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071176:Signaling Lymphocytic Activation Molecule Family
D015703:Antigens, CD; C084093:CD244 protein, human; D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C112260:NCR1 protein, human; C431710:NCR3 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; D055628:Natural Cytotoxicity Triggering Receptor 3; D011971:Receptors, Immunologic; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071176:Signaling Lymphocytic Activation Molecule Family