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
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.
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.
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.
Injection route and activation by LPS independently determine the ability of DC to activate tumor-specific CD8+ T cells in vivo.
KeywordsRodents Dendritic cells CD8+ T cells Tumor immunity
Carboxy-fluorescein diacetate succinimidyl ester
Phosphate buffered saline
T cell receptor
The authors would like to thank all staff of the Malaghan Institute of Medical Research for constructive suggestions and advice, and the Staff at the Biomedical Research Unit of the Wellington School of Medicine and Malaghan Experimental Research Facility for animal husbandry and care. This work was supported by a research grant from the Cancer Society of NZ to FR, and from equipment grants from the NZ Lottery Health Board and the Wellcome Trust. Financial support from the Health Research Council of NZ is also acknowledged. The authors declare no conflicting financial interests.
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