IL-18–induced CD83+CCR7+ NK helper cells

RB Mailliard, SM Alber, H Shen, SC Watkins… - The Journal of …, 2005 - rupress.org
RB Mailliard, SM Alber, H Shen, SC Watkins, JM Kirkwood, RB Herberman, P Kalinski
The Journal of experimental medicine, 2005rupress.org
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 …
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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