Coordinate Expression of Cytokines and Chemokines by NK Cells during Murine Cytomegalovirus Infection

Brigitte G. Dorner, Hamish R.C. Smith, Anthony R. French, Sung Jin Kim, Jennifer Poursine-Laurent, Diana L. Beckman, Jeanette T. Pingel, Richard A. Kroczek, Wayne M. Yokoyama

Research output: Contribution to journalArticlepeer-review

102 Scopus citations


Cytokines and chemokines activate and direct effector cells during infection. We previously identified a functional group of five cytokines and chemokines, namely, IFN-γ, activation-induced T cell-derived and chemokine-related cytokine/lymphotactin, macrophage-inflammatory protein 1α, macrophage-inflammatory protein 1β, and RANTES, coexpressed in individual activated NK cells, CD8+ T cells, and CD4+ Th1 cells in vitro and during in vivo infections. However, the stimuli during infection were not known. In murine CMV (MCMV) infection, the DAP12/KARAP-associated Ly49H NK cell activation receptor is crucial for resistance through recognition of MCMV-encoded m157 but NK cells also undergo in vivo nonspecific responses to uncharacterized stimuli. In this study, we show that Ly49H ligation by m157 resulted in a coordinated release of all five cytokines/ chemokines from Ly49H+ NK cells. Whereas other cytokines also triggered the release of these cytokines/chemokines, stimulation was not confined to the Ly49H+ population. At the single-cell level, the production of the five mediators showed strong positive correlation with each other. Interestingly, NK cells were a major source of these five cytokines/chemokines in vitro and in vivo, whereas infected macrophages produced only limited amounts of macrophage-inflammatory protein 1α, macrophage-inflammatory protein1β, and RANTES. These findings suggest that both virus-specific and nonspecific NK cells play crucial roles in activating and directing other inflammatory cells during MCMV infection.

Original languageEnglish (US)
Pages (from-to)3119-3131
Number of pages13
JournalJournal of Immunology
Issue number5
StatePublished - Mar 1 2004
Externally publishedYes

ASJC Scopus subject areas

  • Immunology


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