Proinflammatory cytokine signaling required for the generation of natural killer cell memory

Joseph C. Sun, Sharline Madera, Natalie A. Bezman, Joshua N. Beilke, Mark Kaplan, Lewis L. Lanier

Research output: Contribution to journalArticle

154 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)947-954
Number of pages8
JournalJournal of Experimental Medicine
Volume209
Issue number5
DOIs
StatePublished - May 7 2012

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Natural Killer Cells
Cytokines
Muromegalovirus
Cytomegalovirus Infections
Interleukin-12 Receptors
Cytokine Receptors
Lymphoid Tissue
Virus Diseases
Interleukin-12
Vaccines

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

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Proinflammatory cytokine signaling required for the generation of natural killer cell memory. / Sun, Joseph C.; Madera, Sharline; Bezman, Natalie A.; Beilke, Joshua N.; Kaplan, Mark; Lanier, Lewis L.

In: Journal of Experimental Medicine, Vol. 209, No. 5, 07.05.2012, p. 947-954.

Research output: Contribution to journalArticle

Sun, Joseph C. ; Madera, Sharline ; Bezman, Natalie A. ; Beilke, Joshua N. ; Kaplan, Mark ; Lanier, Lewis L. / Proinflammatory cytokine signaling required for the generation of natural killer cell memory. In: Journal of Experimental Medicine. 2012 ; Vol. 209, No. 5. pp. 947-954.
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