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Cytokine requirements for the growth and development of mouse NK cells in vitro

Lookup NU author(s): Dr Jennifer Toomey, Frances Davison, Professor Colin Brooks

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Abstract

Natural killer (NK) cells arise from immature progenitors present in fetal tissues and adult bone marrow, but the factors responsible for driving the proliferation and differentiation of these progenitors are poorly understood. Mouse NK cells had previously been thought not to express interleukin (IL)-2Rα chains, but we show here that immature and mature mouse NK cells express IL-2Rα chain mRNA and that low levels of IL-2Rα chains can be detected on the surface of immature and mature NK cells provided they are cultured in the absence of IL-2. Despite their potential expression of high-affinity IL-2 receptors, immature NK cells only proliferate if IL-2 is present at extremely high concentrations. Surprisingly, IL-15 can also only support the growth of immature NK cells at high, presumably nonphysiological concentrations. Although NK cells express mRNA for the high-affinity IL-15Rα chain, they also express a variety of alternately spliced transcripts whose protein products could potentially disrupt signaling through IL-15 receptors. The requirement for high concentrations of IL-2 and IL-15 suggests that if these cytokines play any role in the proliferative expansion of NK cells in vivo, they act indirectly via other cells or in cooperation with other factors. In support of the latter possibility, we report that the recently described cytokine IL-21 can markedly enhance the proliferation of immature (and mature) NK cells in the presence of doses of IL-2 and IL-15 that by themselves have little growth-promoting activity.


Publication metadata

Author(s): Toomey JA, Gays F, Foster D, Brooks CG

Publication type: Article

Publication status: Published

Journal: Journal of Leukocyte Biology

Year: 2003

Volume: 74

Issue: 2

Pages: 233-242

Print publication date: 01/08/2003

Online publication date: 22/05/2003

Acceptance date: 02/04/2003

ISSN (print): 0741-5400

ISSN (electronic): 1938-3673

Publisher: Federation of American Societies for Experimental Biology

URL: http://dx.doi.org/10.1189/jlb.0303097

DOI: 10.1189/jlb.0303097

PubMed id: 12885940


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