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

Sung Jin Kim, Koho Iizuka, Hector L. Aguila, Irving L. Weissman, Wayne M. Yokoyama

Research output: Contribution to journalArticle

326 Scopus citations

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 IFNγ 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.

Original languageEnglish (US)
Pages (from-to)2731-2736
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number6
StatePublished - Mar 14 2000
Externally publishedYes

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