Neutrophils Transport Antigen from the Dermis to the Bone Marrow, Initiating a Source of Memory CD8+ T Cells

The bone marrow (BM) has been identified as a possible organ for T cell priming, yet the fundamental mechanisms of a polyclonal immune response in the BM remain unknown. We found that after intradermal injection of modified vaccinia Ankara virus, unexpected sources of newly primed polyclonal virus-specific CD8+, but not CD4+, T cells were localized in the BM and the draining lymph nodes (dLNs) prior to blood circulation. We identified neutrophils as the virus-carrier cells from the dermis to the BM. In both neutrophil-depleted and Ccr1−/− mice, virus-specific BM CD8+ responses were lost. Myeloid antigen-presenting cells were required for BM CD8+ T cell priming. A systems biology analysis of dLN and BM virus-specific CD8+ T cells revealed distinct transcriptional and multifunctional profiles for cells primed in each organ. We provide direct evidence for how antigen is transported to the BM, providing a source of virus-specific memory CD8+ T cells. ► An alternative source of virus-specific CD8+ T cell responses initiate in the bone marrow ► Neutrophils carry MVA in a CCR1-dependent manner from the skin to the bone marrow ► Phagocytic myeloid cells are required for CD8+ T cell priming in the BM ► Antigen-primed CD8+ T cells are qualitatively different from lymph node-primed cells