Volume 2 Supplement 3

Abstracts of the 29th Annual Scientific Meeting of the Society for Immunotherapy of Cancer (SITC)

Open Access

NK cells protect TCR-transgenic mice from developing fetal leukemia

  • Sigrid Dubois1,
  • Jürgen Müller1,
  • Lionel Feigenbaum2 and
  • Thomas A Waldmann1
Journal for ImmunoTherapy of Cancer20142(Suppl 3):P167

DOI: 10.1186/2051-1426-2-S3-P167

Published: 6 November 2014

To investigate the intrinsic effect of IL-15 expression on CD8 responses we generated IL-15-deficient OT1 TCR-transgenic mice. These mice died surprisingly at around six months of age exhibiting grossly enlarged lymph nodes, spleens and thymi. The affected organs harbored mainly CD8+ T cells that were low for MHC class I, expressed CD25 and CD24 as well as the co-stimulatory receptors CD28, ICOS and PD1. This phenotype resembled a sub-population of immature CD8 single-positive thymocytes. These co-stimulatory r eceptor-positive CD8 cells (CD8cor) expanded after transfers into mice that lacked NK cells due to IL-15 inhibition or antibody-mediated cell lysis, and NK cells caused in vivo lysis of CD8cor cells. In contrast, the presence of IL-15-dependent CD8+ T cells had no effect on CD8cor cell expansion. In vivo expansions of CD8cor cells also depended on the presence of CD11c-positive dendritic cells while IL-2 activity was dispensable despite high CD25 expression. These data suggest that NK cells prevent the thymic escape of a sub-population of CD8 single-positive thymocytes and their subsequent malignant transformation in TCR-transgenic mice.

Authors’ Affiliations

(1)
Lymphoid Malignancies Branch/CCR/NCI
(2)
Transgenic Mouse Model Laboratory, LASP, NCI

Copyright

© Dubois et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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