IL-21 induces both rapid maturation of human CD34+ cell precursors towards NK cells and acquisition of surface killer Ig-like receptors.
The NK cell maturation from CD34(+) Lin(-) hematopoietic cell precursors is a complex process that requires the direct contact with stromal cells and/or the synergistic effect of different cytokines. In this study we show that IL-21 is capable of inducing an accelerated NK cell maturation when added to cultures of CD34(+) Lin(-) cells isolated from human cord blood supplemented with IL-15, Flt3-L and SCF. After 25 days of culture, 50% of CD56(+) cells expressed various NK cell markers including the NKp46 and NKp30 triggering receptors, the CD94/NKG2A inhibitory receptor and CD16. At day 35, substantial fractions of NK cells expressed KIR, CD8 and CD2, i.e. surface markers expressed by mature NK cells, that are virtually undetectable in developing NK cells cultured in the absence of IL-21. Remarkably, similar to mature NK cells all these markers were included in the CD56(dim) cell fraction, while the CD56(bright) population was only composed of CD94/NKG2A(-) and CD94/NKG2A(+) cells. Thus, IL-21 allows the induction of a full NK cell maturation in vitro and offers an important tool for dissecting the molecular mechanisms involved in different steps of NK cell maturation and in the acquisition of a mature KIR repertoire.
Sivori
Simona
S
Dipartimento di Medicina Sperimentale, Università di Genova, Genova, Italy.
Cantoni
Claudia
C
Parolini
Silvia
S
Marcenaro
Emanuela
E
Conte
Romana
R
Moretta
Lorenzo
L
Moretta
Alessandro
A
D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis*; D018801:CD2 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D007378:Interleukins / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000502:physiology*; D037181:Lectins, C-Type / Q000032:analysis; D051920:NK Cell Lectin-Like Receptor Subfamily D; D055627:Natural Cytotoxicity Triggering Receptor 1; D011971:Receptors, Immunologic / Q000032:analysis*; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D000098546:Interleukin-21
D015703:Antigens, CD; D018952:Antigens, CD34; D018801:CD2 Antigens; D016827:CD8 Antigens; D007378:Interleukins; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; C112260:NCR1 protein, human; D051920:NK Cell Lectin-Like Receptor Subfamily D; D055627:Natural Cytotoxicity Triggering Receptor 1; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D000098546:Interleukin-21