Abstract
We have evaluated the NK cell antitumor activity in lymphotoxin (LT)-deficient mice. Both NK cell-mediated tumor rejection and protection from experimental metastases were significantly compromised in LT-alpha-deficient mice. Analysis of LT-alpha-deficient mice revealed that the absolute number of alphabetaTCR- NK1.1+ NK cells was reduced in bone marrow and thymus, but with overall proportional decreases in other hemopoietic organs. In addition, the antitumor potential of alphabetaTCR- NK1.1+ cells, as determined by their lytic capacity and perforin expression, was reduced 1.5- to 3-fold in LT-alpha-deficient mice, as compared with wild-type mice. Combined defects in NK cell development and effector function contribute to compromised NK cell antitumor function in LT-alpha-deficient mice.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibody-Dependent Cell Cytotoxicity / genetics
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Gene Targeting*
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Graft Rejection / genetics
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Graft Rejection / immunology
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Histocompatibility Antigens Class I / genetics
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Immunologic Deficiency Syndromes / genetics*
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Immunologic Deficiency Syndromes / immunology*
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Immunologic Deficiency Syndromes / pathology
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Killer Cells, Natural / pathology*
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Lymphocyte Activation / genetics
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Lymphocyte Count
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Lymphotoxin-alpha / genetics*
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Mice
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Neoplasm Transplantation
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Neoplasms, Experimental / genetics
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Neoplasms, Experimental / immunology
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Spleen / immunology
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Spleen / pathology
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Tumor Cells, Cultured
Substances
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Histocompatibility Antigens Class I
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Lymphotoxin-alpha