Identification of a NCR+/NKG2D+/LFA-1(low)/CD94(-) immature human NK cell subset.
CD56(bright) natural killer (NK) cells, generated in vitro from CD34+ hematopoietic progenitor cells, were characterized after a 30-day culture with flt3 ligand plus IL-15. Virtually, all CD56(bright) cells expressed CD117, CD25, natural cytotoxicity receptors (NCRs), NKG2D, CD161, and CD244, while only a subset expressed CD18-CD11a (LFA-1), and CD94 molecule, defining an immature CD56(bright)/NCRs+/NKG2D+/LFA-1(-)/CD94(-) subset. Another small subset of cells expressing CD94 but not LFA-1 integrin was also identified, suggesting that during NK differentiation LFA-1 might be upregulated later than CD94. To verify this hypothesis in vivo, we evaluated the NK cell expression of LFA-1 in both peripheral and umbilical cord blood samples. Interestingly, in these blood fluids, we have identified a lineage negative CD34(-)/LFA-1(low)/NKp46(dim)/NKG2D(dim)/CD94(-) subset that resembled an immature stage of NK cells present in lymph nodes. Altogether, the results indicate that CD18-CD11a integrin, as well as CD11b in mice, may be a useful marker to identify immature stages of NK cell differentiation.
Zamai
Loris
L
Department of Human, Environmental and Natural Sciences, University of Urbino Carlo Bo, Urbino, Italy. loris.zamai@uniurb.it
Galeotti
Laura
L
Del Zotto
Genny
G
Canonico
Barbara
B
Mirandola
Prisco
P
Papa
Stefano
S
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D040881:CD11a Antigen / Q000096:biosynthesis; D039481:CD11b Antigen / Q000096:biosynthesis; D018821:CD18 Antigens / Q000096:biosynthesis; D002448:Cell Adhesion; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000166:cytology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000096:biosynthesis*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000096:biosynthesis; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D000071176:Signaling Lymphocytic Activation Molecule Family; D013997:Time Factors
D015703:Antigens, CD; D040881:CD11a Antigen; D039481:CD11b Antigen; D018821:CD18 Antigens; C084093:CD244 protein, human; D019409:Interleukin-15; D053645:Interleukin-2 Receptor alpha Subunit; D016169:Lymphocyte Function-Associated Antigen-1; D008565:Membrane Proteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; C084881:flt3 ligand protein; D019009:Proto-Oncogene Proteins c-kit