Adhesion mediated by LFA-1 is required for efficient IL-12-induced NK and NKT cell cytotoxicity.
Interleukin 12 (IL-12)-activated NK1.1+TCRalpha beta+ (NKT2) and NK1.1+TCRalpha beta- (NK) cells exhibit cytotoxic activity against a wide variety of tumor cells in the absence of prior sensitization. Here we demonstrate that the integrin adhesion receptor LFA-1 (CD11a/CD18) regulates the cytotoxic activity of IL-12-activated NKT and NK cells against YAC-1 and EL-4 tumor cells. Differentiation in vivo and the expression of the cytolytic effector molecules perforin and Fas-L were comparable in both IL-12-activated NKT and NK cells from LFA-1-/ - and LFA-1+/+ mice. However, LFA-1-/-IL-12-activated NKT and NK cells showed impaired conjugate formation with target cells. These results provide the first genetic evidence for a role for an adhesion receptor in killing by IL-12-activated NK cells.
Matsumoto
G
G
Amgen Institute, Ontario Cancer Institute, and Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, Canada.
Omi
Y
Y
Lee
U
U
Nishimura
T
T
Shindo
J
J
Penninger
J M
JM
D000818:Animals; D000941:Antigens / Q000032:analysis*; D000950:Antigens, Ly; D000954:Antigens, Surface; D002448:Cell Adhesion; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D018664:Interleukin-12 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000502:physiology; D037181:Lectins, C-Type; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins / Q000032:analysis*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054353:Perforin; D018664:Interleukin-12