title: Enhancement of natural killer activity by an antibody to CD44.
abstract: In this study, we examined the in vitro effect of an anti-CD44 mAb, S5, on NK function using canine PBMC as effectors. S5 enhanced NK activity in a dose-dependent and rapid fashion as did IM7, another anti-CD44 mAb that recognizes a common epitope(s) on CD44. Other anti-CD44 mAb (Hermes-1 and S3) that recognize epitopes distinct from S5 and IM7 had a variable effect on NK activity. The activation of increased killing by S5 only occurred when NK-sensitive targets were used, suggesting that lymphokine-activated killer cells were not being induced. Antibody-dependent cell cytotoxicity was not the mechanism involved in the augmentation of NK activity, nor was it Fc receptor-dependent, inasmuch as S5 F(ab')2 was able to increase NK activity. F(ab') fragments of S5 were equivalent to intact S5 in their ability to stimulate NK activity, demonstrating that cross-linking of CD44 was not a necessary component of stimulation, and that nonspecific agglutination of target and effector cells was not occurring via the two F(ab) arms. The enhancement of NK function was monocyte-independent and mediated by radioresistant cells, indicating that the antibody enhanced NK cells directly. This finding would suggest that CD44 can direct a transmembrane signal for NK cell activation.
authors.affiliation: Transplantation Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
authors.forename: P H
authors.initials: PH
authors.lastname: Tan
authors.forename: E B
authors.initials: EB
authors.lastname: Santos
authors.forename: H C
authors.initials: HC
authors.lastname: Rossbach
authors.forename: B M
authors.initials: BM
authors.lastname: Sandmaier
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D002460:Cell Line; D004285:Dogs; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D009000:Monocytes / Q000502:physiology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D016201:Receptors, Lymphocyte Homing