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International Immunology, Vol. 16, No. 1, pp. 23-32, January 2004
© 2004 Japanese Society for Immunology

Differential regulation of NK cell proliferation by type I and type II IFN

Matthew J. Loza1 and Bice Perussia1

1 Department of Microbiology and Immunology, Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 19107, USA

Correspondence to: B. Perussia; E-mail: Bice.Perussia{at}mail.tju.edu
Transmitting editor: R. Schreiber

IFN, produced during viral infections by accessory (type I IFN) or NK cells (type II IFN), play a primary role in the regulation of immune and anti-viral NK cell effector functions. Because IFN have anti-proliferative effects on several cell types, including hematopoietic cells, we asked whether they modulate proliferation of human NK cells, and whether IFN-{alpha} and IFN-{gamma} mediate distinct effects on NK cells at different developmental stages. Analysis of proliferation at the single-cell level in human NK cells indicated that both IFN types inhibit IL-4-induced accumulation of immature CD56– IL-13+ NK cells in freshly separated peripheral blood lymphocytes and in cells derived from them after short-term cultures. However, IFN-{gamma} inhibited specifically the IL-4-dependent proliferation of these cells without affecting the IL-2-dependent one or that of the IL-13– cells, whereas IFN-{alpha} attenuated proliferation of NK cells at any developmental stage (both immature CD56–IL-13+ and mature CD56+IL-13– IFN-{gamma}+ NK cells) and contributed to their monokine-induced differentiation to IFN-{gamma}-producing cells. Adding to our previous report that IL-13 inhibits accumulation of mature IFN-{gamma}+ NK cells, the present data unravel a mechanism by which peripheral immature IL-13+ and mature IFN-{gamma}+ NK cells can negatively regulate each other’s accumulation.

Keywords: cytokine, NK cell development


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