Tissue-specific homing and expansion of donor NK cells in allogeneic bone marrow transplantation.
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.
Olson
Janelle A
JA
Department of Medicine, Division of Blood and Marrow Transplantation, Stanford University, Stanford, CA 94305, USA.
Zeiser
Robert
R
Beilhack
Andreas
A
Goldman
Joshua J
JJ
Negrin
Robert S
RS
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement / Q000276:immunology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D006086:Graft vs Host Disease / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000008:administration & dosage; D007694:Killer Cells, Natural / Q000166:cytology* / Q000201:enzymology / Q000637:transplantation*; D019041:L-Selectin / Q000502:physiology; D008156:Luciferases / Q000096:biosynthesis; D008221:Lymphoid Tissue / Q000166:cytology* / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity / Q000276:immunology; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D007376:Interleukin-2; D019041:L-Selectin; D008156:Luciferases