Differential regulation of NK cell proliferation by type I and type II IFN.
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.
Loza
Matthew J
MJ
Department of Microbiology and Immunology, Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 19107, USA.
Perussia
Bice
B
D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007107:Immune System / Q000254:growth & development; D007231:Infant, Newborn; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism; D019409:Interleukin-15 / Q000276:immunology / Q000494:pharmacology; D020382:Interleukin-18 / Q000276:immunology / Q000494:pharmacology; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
D007370:Interferon Type I; D018793:Interleukin-13; D019409:Interleukin-15; D020382:Interleukin-18; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma