Interaction between human NK cells and bone marrow stromal cells induces NK cell triggering: role of NKp30 and NKG2D receptors.
In this study we have analyzed the interaction between in vitro cultured bone marrow stromal cells (BMSC) and NK cells. Ex vivo-isolated NK cells neoexpressed the activation Ag CD69 and released IFN-gamma and TNF-alpha upon binding with BMSC. Production of these proinflammatory cytokines was dependent on ligation of ICAM1 expressed on BMSC and its receptor LFA1 on NK cells. Furthermore, the NKp30, among natural cytotoxicity receptors, appeared to be primarily involved in triggering NK cells upon interaction with BMSC. Unexpectedly, autologous IL-2-activated NK cells killed BMSC. Again, LFA1/ICAM1 interaction plays a key role in NK/BMSC interaction; this interaction is followed by a strong intracellular calcium increase in NK cells. More importantly, NKG2D/MHC-I-related stress-inducible molecule A and/or NKG2D/UL-16 binding protein 3 engagement is responsible for the delivery of a lethal hit. It appears that HLA-I molecules do not protect BMSC from NK cell-mediated injury. Thus, NK cells, activated upon binding with BMSC, may regulate BMSC survival.
Poggi
Alessandro
A
Laboratory of Experimental Oncology D, National Cancer Research Institute, Genoa, Italy. alessandro.poggi@istge.it
Prevosto
Claudia
C
Massaro
Anna-Maria
AM
Negrini
Simone
S
Urbani
Serena
S
Pierri
Ivana
I
Saccardi
Riccardo
R
Gobbi
Marco
M
Zocchi
Maria Raffaella
MR
D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000276:immunology*; D020013:Calcium Signaling; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication; D003602:Cytotoxicity, Immunologic; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055628:Natural Cytotoxicity Triggering Receptor 3; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D017154:Stromal Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002352:Carrier Proteins; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D018799:Intercellular Adhesion Molecule-1; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma; D007376:Interleukin-2; D037181:Lectins, C-Type; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055628:Natural Cytotoxicity Triggering Receptor 3; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; C431710:NCR3 protein, human; C423229:ULBP3 protein, human