Proinflammatory cytokine signaling required for the generation of natural killer cell memory Journal Article
| Authors: | Sun, J. C.; Madera, S.; Bezman, N. A.; Beilke, J. N.; Kaplan, M. H.; Lanier, L. L. |
| Article Title: | Proinflammatory cytokine signaling required for the generation of natural killer cell memory |
| Abstract: | Although natural killer (NK) cells are classified as innate immune cells, recent studies demonstrate that NK cells can become long-lived memory cells and contribute to secondary immune responses. The precise signals that promote generation of long-lived memory NK cells are unknown. Using cytokine receptor-deficient mice, we show that interleukin-12 (IL-12) is indispensible for mouse cytomegalovirus (MCMV)-specific NK cell expansion and generation of memory NK cells. In contrast to wild-type NK cells that proliferated robustly and resided in lymphoid and nonlymphoid tissues for months after MCMV infection, IL-12 receptor-deficient NK cells failed to expand and were unable to mediate protection after MCMV challenge. We further demonstrate that a STAT4-dependent IFN-γ-independent mechanism contributes toward the generation of memory NK cells during MCMV infection. Understanding the full contribution of inflammatory cytokine signaling to the NK cell response against viral infection will be of interest for the development of vaccines and therapeutics. |
| Keywords: | signal transduction; controlled study; genetics; nonhuman; flow cytometry; lymphocyte proliferation; animal cell; mouse; phenotype; animal; mouse mutant; animals; mice; mice, knockout; animal experiment; animal model; wild type; mice, inbred c57bl; physiology; c57bl mouse; cytokine; immunology; cytokines; gamma interferon; cellular distribution; natural killer cell; adoptive transfer; killer cells, natural; cytokine release; lymphoid tissue; statistics, nonparametric; cytomegalovirus infection; cell expansion; interleukin 12; immunologic memory; virus immunity; lymphocytotoxicity; immunological memory; nonparametric test; herpes virus infection; herpesviridae infections; interleukin-12; stat4 protein; stat4 transcription factor; il12rb2 protein, mouse; interleukin 12 receptor; stat4 protein, mouse; muromegalovirus; receptors, interleukin-12 |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 209 |
| Issue: | 5 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2012-05-07 |
| Start Page: | 947 |
| End Page: | 954 |
| Language: | English |
| DOI: | 10.1084/jem.20111760 |
| PUBMED: | 22493516 |
| PROVIDER: | scopus |
| PMCID: | PMC3348098 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 August 2012" - "Source: Scopus" |
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