title: High expression of NKR-P1 is not an absolute requirement for natural killer activity in BDIX rats.
abstract: NKR-P1 has been identified as a triggering structure selectively expressed on rat natural killer (NK) cells and adherent lymphokine-activated killer (A-LAK) cells. In vivo treatment with anti-NKR-P1 monoclonal antibody (mAb 3.2.3) was shown to induce complete inhibition of NK cytotoxicity and elimination of LAK cell precursors in Lewis and Fisher rat strains. We investigated the effects of mAb 3.2.3 in a colon tumor model in BDIX rats. Inoculation of animals with mAb 3.2.3 even at very high doses induced a strong but incomplete inhibition of NK cytotoxicity in nylon-wool-non-adherent spleen and peripheral blood cells. Generation of adherent A-LAK cells from their spleen precursors was also strongly by not fully inhibited. We also investigated the effect of treatment with mAb 3.2.3 on the tumorigenicity of the NK-sensitive REGb cell line. When subcutaneously inoculated in syngeneic animals, REGb cells induce tumors that first grow for 2 weeks, then spontaneously regress and disappear. In contrast with previous results using anti-asialoGM1, no significant difference in tumor growth was observed between rats treated with mAB 3.2.3 and control animals, even with a long-term treatment. In vitro, mAb 3.2.3 exhibited the same incomplete efficiency. Nylon-wool-non-adherent spleen cells treated with mAb 3.2.3 plus complement were completely free of 3.2.3(bright) cells, but retained a substantial NK activity and generated LAK cells after culture with IL-2. After an overnight incubation in standard medium of 3.2.3-depleted spleen cells, 3.2.3(bright) cells were partially recovered and the NK cytotoxic activity, as well as the generation of LAK cells, was significantly enhanced. These results suggest that a strong expression of NKR-P1 is not required for BDIX mononuclear cells to exhibit NK function and generate LAK cells under IL-2 activation.
authors.affiliation: EPHE: Cancer Immunotherapy Research Laboratory, Faculté de Médecine, Dijon, France.
authors.forename: D
authors.initials: D
authors.lastname: Pinard
authors.forename: N O
authors.initials: NO
authors.lastname: Olsson
authors.forename: W H
authors.initials: WH
authors.lastname: Chambers
authors.forename: F
authors.initials: F
authors.lastname: Martin
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000276:immunology; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D016207:Cytokines / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D007167:Immunotherapy; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D037181:Lectins, C-Type; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D055651:NK Cell Lectin-Like Receptor Subfamily B; D009368:Neoplasm Transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D016207:Cytokines; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B