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PMID: 10694580 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

In vivo natural killer cell activities revealed by natural killer cell-deficient mice.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 6 ·2000-03-14 ·Pages 2731-6

Kim S, Iizuka K, Aguila HL, Weissman IL, Yokoyama WM

Abstract

Studies of natural killer (NK) cell function in vivo have been challenging primarily due to the lack of animal models in which NK cells are genetically and selectively deficient. Here, we describe a transgenic mouse with defective natural killing and selective deficiency in NK1.1(+) CD3(-) cells. Despite functionally normal B, T, and NK/T cells, transgenic mice displayed impaired acute in vivo rejection of tumor cells. Adoptive transfer experiments confirmed that NK1.1(+) CD3(-) cells were responsible for acute tumor rejection, establishing the relationship of NK1.1(+) CD3(-) cells to NK cells. Additional studies provided evidence that (i) NK cells play an important role in suppressing tumor metastasis and outgrowth; (ii) NK cells are major producers of IFNgamma in response to bacterial endotoxin but not to interleukin-12, and; (iii) NK cells are not essential for humoral responses to T cell-independent type 2 antigen or the generalized Shwartzman reaction, both of which were previously proposed to involve NK cells.

MeSH Terms
Animals CD3 Complex/metabolism Cell Line Flow Cytometry Immunoglobulins/immunology Interferon-gamma/biosynthesis Interleukin-12/pharmacology Killer Cells, Natural/immunology,physiology Lipopolysaccharides/pharmacology Lung Neoplasms/immunology Mice Mice, Inbred C57BL Mice, Transgenic Neoplasm Metastasis/immunology Neoplasm Transplantation Spleen/metabolism Time Factors
Chemicals
CD3 Complex Immunoglobulins Lipopolysaccharides Interleukin-12 Interferon-gamma
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kim S
Howard Hughes Medical Institute, Rheumatology Division, Box 8045, Washington University School of Medicine, St. Louis, MO 63110, USA.
Iizuka K
Aguila H L
Weissman I L
Yokoyama W M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.050588297
Published
2000-03-14
Pages
2731-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC15998
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.050588297 PMC Full Text View journal details
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