NKG2D is a costimulatory receptor for human naive CD8+ T cells.
In humans, all alpha beta CD8+ T cells express NKG2D, but in mouse, it is only expressed by activated and memory CD8+ T cells. We purified human naive CD8+ T cells to show that NKG2D serves as a costimulatory receptor for TCR induced Ca2+ mobilization and proliferation. The resulting effector cells are skewed toward a type 1 phenotype and produce high levels of IFN-gamma and TNF-alpha. NKG2D ligands, MHC class I chain-related (MIC)A, MICB, and UL16-binding proteins are expressed on the proliferating cells and NKG2D is down-regulated. The addition of the homeostatic cytokines IL-7 and IL-15 to the culture medium not only enhances proliferation but also counteracts the down-regulation of NKG2D, more so than the addition of IL-2. These results indicate that NKG2D can regulate the priming of human naive CD8+ T cells, which may provide an alternative mechanism for potentiating and channeling the immune response.
Maasho
Kerima
K
Receptor Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852-1742, USA.
Opoku-Anane
Jessica
J
Marusina
Alina I
AI
Coligan
John E
JE
Borrego
Francisco
F
D000818:Animals; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D020013:Calcium Signaling; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D018076:DNA, Complementary / Q000235:genetics; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation; D008565:Membrane Proteins; D051379:Mice; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology*; D055607:Receptors, Natural Killer Cell; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D002352:Carrier Proteins; D018076:DNA, Complementary; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008024:Ligands; C099187:MHC class I-related chain A; C098080:MICB antigen; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D014409:Tumor Necrosis Factor-alpha; C423231:ULBP1 protein, human; C423230:ULBP2 protein, human; C423229:ULBP3 protein, human; D007371:Interferon-gamma