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. 2004 Mar 1;172(5):3119-31.
doi: 10.4049/jimmunol.172.5.3119.

Coordinate expression of cytokines and chemokines by NK cells during murine cytomegalovirus infection

Brigitte G Dorner  1 , Hamish R C Smith, Anthony R French, Sungjin Kim, Jennifer Poursine-Laurent, Diana L Beckman, Jeanette T Pingel, Richard A Kroczek, Wayne M Yokoyama
Affiliations

Coordinate expression of cytokines and chemokines by NK cells during murine cytomegalovirus infection

Brigitte G Dorner et al. J Immunol. .

Abstract

Cytokines and chemokines activate and direct effector cells during infection. We previously identified a functional group of five cytokines and chemokines, namely, IFN-gamma, activation-induced T cell-derived and chemokine-related cytokine/lymphotactin, macrophage-inflammatory protein 1alpha, macrophage-inflammatory protein 1beta, 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 1alpha, macrophage-inflammatory protein1beta, 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.

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