4.8 Article

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

Journal

IMMUNITY
Volume 37, Issue 5, Pages 917-929

Publisher

CELL PRESS
DOI: 10.1016/j.immuni.2012.07.015

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Funding

  1. Fondation pour la recherche Medicale
  2. European commission [241904]
  3. ANRS (Agence Nationale de Recherche sur le Sida)
  4. INSERM (Institut national de la sante et de la recherche medicale)

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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.

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