CD45-negative mutants of a rat natural killer cell line fail to lyse tumor target cells.
To examine the role of CD45 in NK cell activation, we isolated three mutants and one variant of a rat NK cell line, RNK-16. Each of these lacked cell-surface expression of CD45 and did not have detectable transcripts for CD45 on Northern blot analysis. The CD45-negative cells expressed CD2, CD53, and NKR-P1, but mAb-induced perturbations of these molecules did not induce protein tyrosine phosphorylations and increases in the concentration of cytoplasmic-free calcium, as occurred in the wild-type RNK-16. Unlike the wild-type cells, the CD45-negative cells failed to lyse YAC-1 and RL-male-1 tumor targets. The cytolytic activity of the CD45-negative cells could be stimulated pharmacologically by ionomycin and PMA, which, when added to the cytotoxicity assays, induced killing of tumor targets. These studies suggest that CD45 is required for the response of RNK-16 cells to target cells and for signaling through CD2, CD53, and NKR-P1.
Bell
G M
GM
Department of Medicine, San Francisco VA Medical Center, CA.
Dethloff
G M
GM
Imboden
J B
JB
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D018801:CD2 Antigens; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D007694:Killer Cells, Natural / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000032:analysis*; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D051381:Rats; D011971:Receptors, Immunologic / Q000502:physiology; D060265:Tetraspanin 25
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; C554896:Cd53 protein, rat; D011971:Receptors, Immunologic; D060265:Tetraspanin 25; D011505:Protein-Tyrosine Kinases; D017493:Leukocyte Common Antigens