TY - JOUR
T1 - Novel APC-like properties of human NK cells directly regulate T cell activation
AU - Hanna, Jacob
AU - Gonen-Gross, Tsufit
AU - Fitchett, Jonathan
AU - Rowe, Tony
AU - Daniels, Mark
AU - Arnon, Tal I.
AU - Gazit, Roi
AU - Joseph, Aviva
AU - Schjetne, Karoline W.
AU - Steinle, Alexander
AU - Porgador, Angel
AU - Mevorach, Dror
AU - Goldman-Wohl, Debra
AU - Yagel, Simcha
AU - LaBarre, Michael J.
AU - Buckner, Jane H.
AU - Mandelboim, Ofer
PY - 2004/12
Y1 - 2004/12
N2 - Initiation of the adaptive immune response is dependent on the priming of naive T cells by APCs. Proteomic analysis of unactivated and activated human NK cell membrane-enriched fractions demonstrated that activated NK cells can efficiently stimulate T cells, since they upregulate MHC class II molecules and multiple ligands for TCR costimulatory molecules. Furthermore, by manipulating antigen administration, we show that NK cells possess multiple independent unique pathways for antigen uptake. These results highlight NK cell-mediated cytotoxicity and specific ligand recognition by cell sur face-activating receptors on NK cells as unique mechanisms for antigen capturing and presentation. In addition, we analyzed the T cell-activating potential of human NK cells derived from different clinical conditions, such as inflamed tonsils and noninfected and CMV-infected uterine decidual samples, and from transporter-associated processing antigen 2-deficient patients. This in vivo analysis revealed that proinflammatory, but not immune-suppressive, microenvironmental requirements can selectively dictate upregulation of T cell-activating molecules on NK cells. Taken together, these observations offer new and unexpected insights into the direct interactions between NK and T cells and suggest novel APC-like activating functions for human NK cells.
AB - Initiation of the adaptive immune response is dependent on the priming of naive T cells by APCs. Proteomic analysis of unactivated and activated human NK cell membrane-enriched fractions demonstrated that activated NK cells can efficiently stimulate T cells, since they upregulate MHC class II molecules and multiple ligands for TCR costimulatory molecules. Furthermore, by manipulating antigen administration, we show that NK cells possess multiple independent unique pathways for antigen uptake. These results highlight NK cell-mediated cytotoxicity and specific ligand recognition by cell sur face-activating receptors on NK cells as unique mechanisms for antigen capturing and presentation. In addition, we analyzed the T cell-activating potential of human NK cells derived from different clinical conditions, such as inflamed tonsils and noninfected and CMV-infected uterine decidual samples, and from transporter-associated processing antigen 2-deficient patients. This in vivo analysis revealed that proinflammatory, but not immune-suppressive, microenvironmental requirements can selectively dictate upregulation of T cell-activating molecules on NK cells. Taken together, these observations offer new and unexpected insights into the direct interactions between NK and T cells and suggest novel APC-like activating functions for human NK cells.
UR - http://www.scopus.com/inward/record.url?scp=85047690749&partnerID=8YFLogxK
U2 - 10.1172/JCI22787
DO - 10.1172/JCI22787
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C2 - 15578093
AN - SCOPUS:85047690749
SN - 0021-9738
VL - 114
SP - 1612
EP - 1623
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 11
ER -