Affordable Access

deepdyve-link
Publisher Website

Tissue-specific homing and expansion of donor NK cells in allogeneic bone marrow transplantation.

Authors
  • Olson, Janelle A
  • Zeiser, Robert
  • Beilhack, Andreas
  • Goldman, Joshua J
  • Negrin, Robert S
Type
Published Article
Journal
The Journal of Immunology
Publisher
The American Association of Immunologists
Publication Date
Sep 01, 2009
Volume
183
Issue
5
Pages
3219–3228
Identifiers
DOI: 10.4049/jimmunol.0804268
PMID: 19657090
Source
Medline
License
Unknown

Abstract

NK cells have potential therapeutic impact in suppressing graft-versus-host disease (GVHD) and enhancing antitumor effects as a cellular therapy for hematologic malignancies. However, few studies have addressed the trafficking and in vivo behavior of NK cells in murine models of bone marrow transplantation (BMT). We investigated NK cell trafficking and survival following allogeneic and syngeneic BMT using a novel bioluminescence-based imaging strategy. Transplantation of luciferase-expressing NK cells revealed CD62L-mediated trafficking to lymphoid organs and trafficking to GVHD target tissues, as evidenced by in vivo and ex vivo bioluminescence imaging. The NK cells persisted for approximately 4 wk after transplantation in allogeneic recipients, but were not detectable in syngeneic recipients. CFSE-labeling studies showed extensive NK cell proliferation in vivo. Transplanted NK cells up-regulated molecules necessary for homing to the lymph nodes, gastrointestinal tract, and skin, yet did not cause clinical GVHD. This expansion and tissue-specific homing was not solely due to the conditioning regimen, as NK cells proliferated and reached lymphoid and GVHD target tissue in unconditioned allogeneic RAG2(-/-) gamma-chain(-/-) recipients. IL-2 enhanced expansion and antitumor activity of NK cells. These results provide significant insight into the behavior and potential therapeutic impact of NK cells in BMT.

Report this publication

Statistics

Seen <100 times