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Bone marrow as a priming site for T-cell responses to blood-borne antigen

Nature Medicine volume 9, pages 1151–1157 (2003)Cite this article

Abstract

Although bone marrow is known as a primary lymphoid organ, its potential to serve as a secondary immune organ has hardly been explored. Here we demonstrate that naive, antigen-specific T cells home to bone marrow, where they can be primed. Antigen presentation to T cells in bone marrow is mediated via resident CD11c+ dendritic cells. They are highly efficient in taking up exogenous blood-borne antigen and processing it via major histocompatibility complex class I and class II pathways. T-cell activation correlates with dendritic cell–T cell clustering in bone marrow stroma. Primary CD4+ and CD8+ T-cell responses generated in bone marrow occur in the absence of secondary lymphoid organs. The responses are not tolerogenic and result in generation of cytotoxic T cells, protective anti-tumor immunity and immunological memory. These findings highlight the uniqueness of bone marrow as an organ important for hemato- and lymphopoiesis and for systemic T cell–mediated immunity.

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Figure 1: Homing of naive T cells to bone marrow.
Figure 2: Antigen-presenting capacity of resident dendritic cells in bone marrow.
Figure 3: Primary T-cell response in bone marrow.
Figure 4: Cluster formation between T cells and antigen-presenting dendritic cells in bone marrow.
Figure 5: Generation of cytotoxic T cells in bone marrow of mice lacking secondary lymphoid organs and its dependence on T-cell homing to bone marrow.
Figure 6: Protective systemic antitumor immunity in mice lacking secondary lymphoid organs.

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Acknowledgements

We thank T. Schüler and K. Hogquist for OT-I/Rag1−/− mice; R. Zinkernagel for Map3k14aly/aly mice; G. Moldenhauer and P. Altevogt for antibodies; G. Kübelbeck and K. Tauber for RMA-OVA cells; P. Angel for a construct with a ubiquitin promoter; A. Griesbach for mouse splenectomy; K. Hexel for help with cell sorting; M. Gehring for technical assistance; and H. Müssig for secretarial assistance. We thank the NIAID Tetramer Facility and NIH AIDS Research and Reference Reagent Program for providing H-2Ld/peptide tetrameric complexes. We thank the M. Scheel-Stiftung (no. 10-1589-Schi5) for financial support.

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Author notes

  1. Viktor Umansky

    Present address: Clinical Cooperation Unit Dermato-Oncology, DKFZ, Heidelberg, Germany

  2. Markus Feuerer, Philipp Beckhove and Natalio Garbi: These authors contributed equally to this work.

Authors and Affiliations

  1. Tumor Immunology Program, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Markus Feuerer, Philipp Beckhove, Natalio Garbi, Yolanda Mahnke, Mirja Hommel, Günter J Hämmerling, Bruno Kyewski, Viktor Umansky & Volker Schirrmacher

  2. Institute for Molecular Medicine and Experimental Immunology, University Clinic, Bonn, Germany

    Andreas Limmer

  3. Department of Experimental Rheumatology, Medical Clinic, Charité, Humboldt University, Berlin, Germany

    Alf Hamann

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Feuerer, M., Beckhove, P., Garbi, N. et al. Bone marrow as a priming site for T-cell responses to blood-borne antigen. Nat Med 9, 1151–1157 (2003). https://doi.org/10.1038/nm914

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