¹Toomey, J.A., ¹Gays, F., ²Foster, D., and ¹Brooks, C.G.
¹School of Cell and Molecular Biosciences, The Medical School, Newcastle, U.K.; and ²Department of Functional Cloning, ZymoGenetics Inc., Seattle, U.S.A.

Submitted, 2003.
 

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 IL2Ra chains but we show here that both immature and mature mouse NK cells express IL2Ra chain mRNA, and that low levels of IL2Ra chains can be detected on the surface of immature and mature NK cells provided they are cultured in the absence of IL2.  Despite their potential expression of high affinity IL2 receptors, immature NK cells only proliferate if IL2 is present at extremely high concentrations.  Surprisingly, IL15 can also only support the growth of immature NK cells at high, presumably non-physiological, concentrations.  Although NK cells express mRNA for the high affinity IL15Ra chain, they also express a variety of alternately spliced transcripts whose protein products could potentially disrupt signaling through IL15 receptors.  The requirement for high concentrations of IL2 and IL15 suggests that if these cytokines play any role in the proliferative expansion of NK cells in vivo they either act indirectly via other cells or in cooperation with other factors.  In support of the latter possibility, we report that the recently described cytokine IL21 can markedly enhance the proliferation of immature [and mature] NK cells in the presence of doses of IL2 and IL15 that by themselves have little growth promoting activity. Key Data