A role for lymphotoxin in the acquisition of Ly49 receptors during NK cell development

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Abstract
NK cells lyse tumor, virus‐infected and allogeneic cells through a recognition system involving inhibitory and activating receptors, among which are the Ly49 molecules that recognize MHC class I proteins. To date, little is known about the regulation of Ly49 expression during NK cell development. In this study we report that the acquisition of Ly49 receptors by NK cells is significantly reduced in lymphotoxin (LT) α‐deficient mice, whereas it is increased in LTα transgenic mice. Treating normal mice with LTβR‐Ig fusion protein reduced Ly49 expression, indicating that regulation of Ly49 receptor expression occurs through the engagement of membrane LT to LTβR, and not soluble LT to TNFR. In addition, when LTα–/– mice were treated exogenously with recombinant IL‐15, NK cell numbers as well as Ly49 acquisition were restored to wild‐type levels. Finally, using real‐time PCR analyses of bone marrow cells obtained from LT‐deficient or transgenic mice, we show a direct correlation between LTβR activation and increased IL‐15 transcription. These data suggest that LTβR‐mediated signals regulate Ly49 expression at least in part through the activation of IL‐15.