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Blood, 15 May 2001, Vol. 97, No. 10, pp. 3146-3151

IMMUNOBIOLOGY

Human natural killer cells: a unique innate immunoregulatory role for the CD56bright subset

Megan A. Cooper, Todd A. Fehniger, Sarah C. Turner, Kenneth S. Chen, Bobak A. Ghaheri, Tariq Ghayur, William E. Carson, and Michael A. Caligiuri

From the Department of Internal Medicine, Division of Hematology/Oncology; the Department of Molecular Virology, Immunology and Medical Genetics, Division of Human Cancer Genetics; the Department of Surgery; and the Comprehensive Cancer Center, The Ohio State University, Columbus, OH; and BASF Bioresearch Corporation, Worcester, MA.

During the innate immune response to infection, monocyte-derived cytokines (monokines), stimulate natural killer (NK) cells to produce immunoregulatory cytokines that are important to the host's early defense. Human NK cell subsets can be distinguished by CD56 surface density expression (ie, CD56bright and CD56dim). In this report, it is shown that CD56bright NK cells produce significantly greater levels of interferon-gamma , tumor necrosis factor-beta , granulocyte macrophage-colony-stimulating factor, IL-10, and IL-13 protein in response to monokine stimulation than do CD56dim NK cells, which produce negligible amounts of these cytokines. Further, qualitative differences in CD56bright NK-derived cytokines are shown to be dependent on the specific monokines present. For example, the monokine IL-15 appears to be required for type 2 cytokine production by CD56bright NK cells. It is proposed that human CD56bright NK cells have a unique functional role in the innate immune response as the primary source of NK cell-derived immunoregulatory cytokines, regulated in part by differential monokine production.

© 2001 by The American Society of Hematology.
 

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