Cross-talk between activated human NK cells and CD4+ T cells via OX40-OX40 ligand interactions.
It is important to understand which molecules are relevant for linking innate and adaptive immune cells. In this study, we show that OX40 ligand is selectively induced on IL-2, IL-12, or IL-15-activated human NK cells following stimulation through NKG2D, the low affinity receptor for IgG (CD16) or killer cell Ig-like receptor 2DS2. CD16-activated NK cells costimulate TCR-induced proliferation, and IFN-gamma produced by autologous CD4+ T cells and this process is dependent upon expression of OX40 ligand and B7 by the activated NK cells. These findings suggest a novel and unexpected link between the natural and specific immune responses, providing direct evidence for cross-talk between human CD4+ T cells and NK receptor-activated NK cells.
Zingoni
Alessandra
A
Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, CA 94143, USA.
Sornasse
Thierry
T
Cocks
Benjamin G
BG
Tanaka
Yuetsu
Y
Santoni
Angela
A
Lanier
Lewis L
LL
D015703:Antigens, CD / Q000502:physiology; D000954:Antigens, Surface; D018122:B7-1 Antigen / Q000378:metabolism / Q000502:physiology*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000097:blood / Q000502:physiology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000502:physiology; D008565:Membrane Proteins; D020411:Oligonucleotide Array Sequence Analysis; D020239:Receptor Cross-Talk / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011971:Receptors, Immunologic / Q000097:blood / Q000502:physiology; D054340:Receptors, KIR; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology
D015703:Antigens, CD; D000954:Antigens, Surface; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D016207:Cytokines; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; D014409:Tumor Necrosis Factor-alpha