A role for lymphotoxin in the acquisition of Ly49 receptors during NK cell development.
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) alpha-deficient mice, whereas it is increased in LTalpha transgenic mice. Treating normal mice with LTbetaR-Ig fusion protein reduced Ly49 expression, indicating that regulation of Ly49 receptor expression occurs through the engagement of membrane LT to LTbetaR, and not soluble LT to TNFR. In addition, when LTalpha(-/-) 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 LTbetaR activation and increased IL-15 transcription. These data suggest that LTbetaR-mediated signals regulate Ly49 expression at least in part through the activation of IL-15.
Lian
Rebecca H
RH
The Department of Pathology, University of Chicago, Chicago, IL 60637, USA. rlian@bsd.uchicago.edu
Chin
Robert K
RK
Nemeth
Hajnalka E
HE
Libby
Shon L
SL
Fu
Yang-Xin
YX
Kumar
Vinay
V
D000818:Animals; D000950:Antigens, Ly / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D019409:Interleukin-15 / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D055630:Receptors, NK Cell Lectin-Like; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D000950:Antigens, Ly; D019409:Interleukin-15; D037181:Lectins, C-Type; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D055630:Receptors, NK Cell Lectin-Like; D018124:Receptors, Tumor Necrosis Factor