In addition to their cytotoxic activities, natural killer (NK) cells can have immunoregulatory functions. We describe a distinct “helper” differentiation pathway of human CD56+CD3− NK cells into CD56+/CD83+/CCR7+/CD25+ cells that display high migratory responsiveness to lymph node (LN)–associated chemokines, high ability to produce interferon-γ upon exposure to dendritic cell (DC)- or T helper (Th) cell–related signals, and pronounced abilities to promote interleukin (IL)-12p70 production in DCs and the development of Th1 responses. This helper pathway of NK cell differentiation, which is not associated with any enhancement of cytolytic activity, is induced by IL-18, but not other NK cell–activating factors. It is blocked by prostaglandin (PG)E2, a factor that induces a similar CD83+/CCR7+/CD25+ LN-homing phenotype in maturing DCs. The current data demonstrate independent regulation of the “helper” versus “effector” pathways of NK cell differentiation and novel mechanisms of immunoregulation by IL-18 and PGE2.
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3 October 2005
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October 03 2005
IL-18–induced CD83 + CCR7 + NK helper cells
Robbie B. Mailliard,
Robbie B. Mailliard
1Department of Surgery, University of Pittsburgh
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Sean M. Alber,
Sean M. Alber
2Department of Cell Biology and Physiology, University of Pittsburgh
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Hongmei Shen,
Hongmei Shen
3Department of Radiation Oncology, University of Pittsburgh
7University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213
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Simon C. Watkins,
Simon C. Watkins
2Department of Cell Biology and Physiology, University of Pittsburgh
4Department of Immunology, University of Pittsburgh
7University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213
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John M. Kirkwood,
John M. Kirkwood
5Department of Medicine, University of Pittsburgh
7University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213
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Ronald B. Herberman,
Ronald B. Herberman
5Department of Medicine, University of Pittsburgh
7University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213
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Pawel Kalinski
Pawel Kalinski
1Department of Surgery, University of Pittsburgh
4Department of Immunology, University of Pittsburgh
6Department of Infectious Diseases and Microbiology, University of Pittsburgh
7University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213
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Robbie B. Mailliard
1Department of Surgery, University of Pittsburgh
Sean M. Alber
2Department of Cell Biology and Physiology, University of Pittsburgh
Hongmei Shen
3Department of Radiation Oncology, University of Pittsburgh
7University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213
Simon C. Watkins
2Department of Cell Biology and Physiology, University of Pittsburgh
4Department of Immunology, University of Pittsburgh
7University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213
John M. Kirkwood
5Department of Medicine, University of Pittsburgh
7University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213
Ronald B. Herberman
5Department of Medicine, University of Pittsburgh
7University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213
Pawel Kalinski
1Department of Surgery, University of Pittsburgh
4Department of Immunology, University of Pittsburgh
6Department of Infectious Diseases and Microbiology, University of Pittsburgh
7University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213
CORRESPONDENCE Pawel Kalinski: [email protected]
Abbreviations used: Ag, antigen; PG, prostaglandin.
Received:
January 14 2005
Accepted:
August 11 2005
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2005
J Exp Med (2005) 202 (7): 941–953.
Article history
Received:
January 14 2005
Accepted:
August 11 2005
Citation
Robbie B. Mailliard, Sean M. Alber, Hongmei Shen, Simon C. Watkins, John M. Kirkwood, Ronald B. Herberman, Pawel Kalinski; IL-18–induced CD83+CCR7+ NK helper cells . J Exp Med 3 October 2005; 202 (7): 941–953. doi: https://doi.org/10.1084/jem.20050128
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