Differential involvement of CD40, CD80, and major histocompatibility complex class I molecules in cytotoxicity induction and interferon-gamma production by human natural killer effectors.
Natural killer (NK) cells are physiologically involved in the immune response against viruses, intracellular bacteria, and parasites as well as against malignant diseases. In addition to the cytotoxic activity, NK lymphocytes mediate a variety of homeostatic effects by producing cytokines. This study focused on the differential role of CD40 and CD80 costimulatory molecules and major histocompatibility complex class I (MHC-I) antigens in the regulation of cytotoxicity and of interferon (IFN)-gamma secretion of resting and interleukin (IL)-2-activated human NK cells. CD40 and CD80 molecules were observed to play a specific role in the induction of cytotoxic function but not in IFN-gamma production of IL-2-activated NK effectors. In addition, a critical role of CD94-dependent MHC-I recognition for the regulation of IFN-gamma production and target lysis was demonstrated. These data provide a possible mechanism underlying functional interactions between NK lymphocytes and CD40/CD80-expressing cell targets, as represented by dendritic cells.
Terrazzano
Giuseppe
G
Cattedra di Immunologia, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, Italy. terrazza@unina.it
Zanzi
Delia
D
Palomba
Carmen
C
Carbone
Ennio
E
Grimaldi
Serena
S
Pisanti
Simona
S
Fontana
Silvia
S
Zappacosta
Serafino
S
Ruggiero
Giuseppina
G
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology; D015703:Antigens, CD / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000276:immunology*; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000276:immunology
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D018122:B7-1 Antigen; D019013:CD40 Antigens; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011993:Recombinant Fusion Proteins; C073119:TAP1 protein, human; C071692:TAP2 protein, human; D007371:Interferon-gamma