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Interleukin-12-Activated Natural Killer Cells Recognize B7
Costimulatory Molecules on Tumor Cells and Autologous Dendritic Cells
Anja B. Geldhof,
Muriel Moser,
Laurence Lespagnard,
Kris Thielemans, and
Patrick De Baetselier
From the Laboratory of Cellular Immunology, Flanders Interuniversity
Institute for Biotechnology, Vrije Universiteit Brussel (VUB); the
Laboratory of Animal Physiology, Université Libre de Bruxelles
(ULB), Sint-Genesius Rode; and the Laboratory of Physiology, Medical
School, VUB, Jette, Belgium.
Activation of natural killer (NK) cells in the presence of
interleukin-12 (IL-12) augments the capacity of these effector cells to
recognize B7-1- and B7-2-expressing target cells. These effector
cells also efficiently lyse autologous B7-positive progenitor or
organ-derived dendritic cells, suggesting a physiologic regulatory pathway between IL-12, NK cells, and B7-expressing antigen-presenting cells. Although IL-12-activated NK cells secreted higher levels of
interferon- , this cytokine did not play a role in
synergistic effects of IL-12 and B7 on NK activation. The
B7-counterreceptor was found to be selectively upregulated on
IL-2/IL-12 as compared with IL-2-activated NK cells. CD28 is
functionally involved in the recognition of B7 on target cells since
IL-2/IL-12-activated NK cells derived from CD28 knockout mice were
strongly reduced in their capacity to lyse syngeneic B7-positive tumor
cells as well as antigen-presenting cells. However, recognition of B7
on allogeneic targets did not require the expression of CD28 on the IL-2/IL-12-activated NK cells. Hence, IL-12 triggers the expression of
both CD28-dependent and CD28-independent mechanisms that allow NK cells
to eliminate B7-positive target cells including autologous dendritic
cells.
Blood, Vol. 91 No. 1 (January 1), 1998:
pp. 196-206
© 1998 by The American Society of Hematology.
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