High expression of NKR-P1 is not an absolute requirement for natural killer activity in BDIX rats |
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Authors: | Dominique Pinard N-O Olsson William H Chambers François Martin |
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Institution: | (1) EPHE: Cancer Immunotherapy Research Laboratory, Faculté de Médecine, 21033 Dijon, France, FR;(2) Research Group on Gastrointestinal Tumors, Faculté de Médecine, 21033 Dijon, France, FR;(3) Division of Basic Research, Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA, US |
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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 but 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 3.2.3bright 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, 3.2.3bright 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.
Received: 11 July 1995 / Accepted: 16 November 1995 |
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Keywords: | NK cell NKR-P1 Rat Colon tumor Tumor regression |
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