Novel APC-like properties of human NK cells directly regulate T cell activation.
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 surface-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.
Hanna
Jacob
J
The Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Gonen-Gross
Tsufit
T
Fitchett
Jonathan
J
Rowe
Tony
T
Daniels
Mark
M
Arnon
Tal I
TI
Gazit
Roi
R
Joseph
Aviva
A
Schjetne
Karoline W
KW
Steinle
Alexander
A
Porgador
Angel
A
Mevorach
Dror
D
Goldman-Wohl
Debra
D
Yagel
Simcha
S
LaBarre
Michael J
MJ
Buckner
Jane H
JH
Mandelboim
Ofer
O
D000938:Antigen-Presenting Cells / Q000166:cytology / Q000378:metabolism*; D000941:Antigens / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005802:Genes, MHC Class II; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D011247:Pregnancy; D020543:Proteome / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets
D000941:Antigens; D015703:Antigens, CD; D020543:Proteome; D011948:Receptors, Antigen, T-Cell