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Article
Nature Medicine  9, 1151 - 1157 (2003)
Published online: 10 August 2003; | doi:10.1038/nm914

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

Markus Feuerer1, 5, Philipp Beckhove1, 5, Natalio Garbi1, 5, Yolanda Mahnke1, Andreas Limmer2, Mirja Hommel1, Günter J Hämmerling1, Bruno Kyewski1, Alf Hamann3, Viktor Umansky1, 4 & Volker Schirrmacher1

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

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

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

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

5  These authors contributed equally to this work.

Correspondence should be addressed to Volker Schirrmacher V.Schirrmacher@dkfz.de
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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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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