Figure 19.  IL21 can enhance the growth of immature NK cells in the presence of limiting concentrations of IL2 or IL15
IL21 concentration [pM]
One explanation for the requirement for very high, probably non-physiological, doses of IL15 and IL2 for
the growth of NK cells is that these cytokines do not act alone in vivo but in association with other factors.
We therefore examined the ability of a large number of cytokines to enhance the growth of immature and
mature NK cells in the presence of IL15 or IL2.  We found only one cytokine that was able to do so, IL21.
E14 progenitors were grown for 2 days in IL4 + PMA, then transferred to medium containing various
concentrations of IL15, IL2, or no cytokine, together with titrated doses of IL21. Growth was measured
3 days later.
Conclusions
1.  IL21 alone cannot induce the growth of immature NK cells.
2.  However, it exerts a striking biphasic effect on the growth of immature NK cells in IL15 or IL2.
3.  At high concentrations [2nM] it generally causes a strong inhibition of growth.
4.  At low doses, most commonly at ~20pM, it can dramatically enhance the growth of NK cells.
5.  The enhancing effects of IL21 are more marked at low rather than high doses of IL15 and IL21.
6.  Similar effects were found on the growth of mature NK cells [data not shown].