Abstract
Dendritic cells (DCs) carry antigen from peripheral tissues via lymphatics to lymph nodes. We report here that differentiated DCs can also travel from the periphery into the blood. Circulating DCs migrated to the spleen, liver and lung but not lymph nodes. They also homed to the bone marrow, where they were retained better than in most other tissues. Homing of DCs to the bone marrow depended on constitutively expressed vascular cell adhesion molecule 1 and endothelial selectins in bone marrow microvessels. Two-photon intravital microscopy in bone marrow cavities showed that DCs formed stable antigen-dependent contacts with bone marrow–resident central memory T cells. Moreover, using this previously unknown migratory pathway, antigen-pulsed DCs were able to trigger central memory T cell–mediated recall responses in the bone marrow.
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Acknowledgements
We thank A. Vazquez-Torres (University of Colorado) for mutant strains of salmonella; G. Cheng and B. Reinhardt for technical support; and L. Scimone for help with intravital microscopy analysis. Supported by National Institutes of Health (AI061663, HL62524, HL54936 and HL56949 to U.H.v.A.); an Amy Potter fellowship, the Charles Hood Foundation and the Multiple Myeloma Foundation (I.B.M.); and Federazione Italiana Ricerca sul Cancro (R.B.).
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Supplementary Video 1
Representative 3D time-lapse movie generated by 2-photon intravital microscopy in the skull of an anesthetized mouse. Hoechst 33342-labeled (blue) P14 TCM were injected into recipient mice and allowed to distribute in the body. 18h later, CMTMR-labeled (red) purified spleen DC were injected i.v. without peptide pulsing. Two hours thereafter, the animal was prepared for 2-photon intravital microscopy of skull BM as described in Materials and Methods. The luminal compartment of BM microvessels was delineated by i.v. injection of FITC-dextran (2MDa). 3D image stacks (23 optical sections, 5 µm vertical step size) were acquired every minute during a 30 min scan period. The total imaged volume (w x l x d) was 210 µm x 210 µm x 110 µm. (MOV 2880 kb)
Supplementary Video 2
Representative 3D time-lapse movie generated as described for movie 1, except that DC were pulsed with antigenic gp33 peptide prior to injection. Note that most TCM move at reduced velocity and undergo long-lasting tight contacts with DC. (MOV 2936 kb)
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Cavanagh, L., Bonasio, R., Mazo, I. et al. Activation of bone marrow–resident memory T cells by circulating, antigen-bearing dendritic cells. Nat Immunol 6, 1029–1037 (2005). https://doi.org/10.1038/ni1249
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DOI: https://doi.org/10.1038/ni1249
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