title: Activation and route of administration both determine the ability of bone marrow-derived dendritic cells to accumulate in secondary lymphoid organs and prime CD8+ T cells against tumors.
abstract: OBJECTIVE
  To examine the effects of route of administration and activation status on the ability of dendritic cells (DC) to accumulate in secondary lymphoid organs, and induce expansion of CD8(+) T cells and anti-tumor activity.
  
  
  METHODS
  DC from bone marrow (BM) cultures were labeled with fluorochromes and injected s.c. or i.v. into naïve mice to monitor their survival and accumulation in vivo. Percentages of specific CD8(+) T cells in blood and delayed tumor growth were used as readouts of the immune response induced by DC immunization.
  
  
  RESULTS
  The route of DC administration was critical in determining the site of DC accumulation and time of DC persistence in vivo. DC injected s.c. accumulated in the draining lymph node, and DC injected i.v. in the spleen. DC appeared in the lymph node by 24 h after s.c. injection, their numbers peaked at 48 h and declined at 96 h. DC that had spontaneously matured in vitro were better able to migrate compared to immature DC. DC were found in the spleen at 3 h and 24 h after i.v. injection, but their numbers were low and declined by 48 h. Depending on the tumor cell line used, DC injected s.c. were as effective or more effective than DC injected i.v. at inducing anti-tumor responses. Pre-treatment with LPS increased DC accumulation in lymph nodes, but had no detectable effect on accumulation in the spleen. Pre-treatment with LPS also improved the ability of DC to induce CD8(+) T cell expansion and anti-tumor responses, regardless of the route of DC administration.
  
  
  CONCLUSIONS
  Injection route and activation by LPS independently determine the ability of DC to activate tumor-specific CD8(+) T cells in vivo.
authors.affiliation: Malaghan Institute of Medical Research, PO Box 7060, Wellington South, New Zealand.
authors.forename: Stephanie P
authors.initials: SP
authors.lastname: Huck
authors.forename: Shiau-Choot
authors.initials: SC
authors.lastname: Tang
authors.forename: Kate A
authors.initials: KA
authors.lastname: Andrew
authors.forename: Jianping
authors.initials: J
authors.lastname: Yang
authors.forename: Jacquie L
authors.initials: JL
authors.lastname: Harper
authors.forename: Franca
authors.initials: F
authors.lastname: Ronchese
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D002470:Cell Survival; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation / Q000276:immunology*; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*