The activating immunoreceptor NKG2D and its ligands are involved in allograft transplant rejection.
Although the linkage between innate and adaptive immunity in transplantation has been recognized, the mechanisms underlying this cooperation remain to be fully elucidated. In this study, we show that early "danger" signals associated with transplantation lead to rapid up-regulation of NKG2D ligands. A second wave of NKG2D ligand up-regulation is mediated by the adaptive immune response to allografts. Treatment with an Ab to NKG2D was highly effective in preventing CD28-independent rejection of cardiac allografts. Notably, NKG2D blockade did not deplete CD8(+) T cells or NK1.1(+) cells nor affect their migration to the allografts. These results establish a functional role of NKG2D and its ligands in the rejection of solid organ transplants.
Kim
Jim
J
Transplantation Research Laboratory, Division of Transplantation, Department of Surgery, University of California, San Francisco, CA 94143, USA.
Chang
Catherine K
CK
Hayden
Tracy
T
Liu
Feng-Chun
FC
Benjamin
Jonathan
J
Hamerman
Jessica A
JA
Lanier
Lewis L
LL
Kang
Sang-Mo
SM
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D000950:Antigens, Ly; D000954:Antigens, Surface / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D016027:Heart Transplantation / Q000276:immunology*; D007113:Immunity, Innate / Q000187:drug effects; D037181:Lectins, C-Type / Q000276:immunology; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D055651:NK Cell Lectin-Like Receptor Subfamily B; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000276:immunology*; D055607:Receptors, Natural Killer Cell; D014184:Transplantation, Homologous; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D000906:Antibodies; D000950:Antigens, Ly; D000954:Antigens, Surface; D018106:CD28 Antigens; C527211:Klrb1c protein, mouse; C527086:Klrk1 protein, mouse; D037181:Lectins, C-Type; D008024:Ligands; D055651:NK Cell Lectin-Like Receptor Subfamily B; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell