Bone marrow as a priming site for T-cell responses to blood-borne antigen.
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.
Feuerer
Markus
M
Tumor Immunology Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Beckhove
Philipp
P
Garbi
Natalio
N
Mahnke
Yolanda
Y
Limmer
Andreas
A
Hommel
Mirja
M
Hämmerling
Günter J
GJ
Kyewski
Bruno
B
Hamann
Alf
A
Umansky
Viktor
V
Schirrmacher
Volker
V
D000818:Animals; D000941:Antigens / Q000097:blood*; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007156:Immunologic Memory / Q000276:immunology; D037181:Lectins, C-Type; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013156:Splenectomy; D013601:T-Lymphocytes / Q000276:immunology*; D000099192:CD69 Antigens
D000941:Antigens; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D039521:CD11c Antigen; D037181:Lectins, C-Type; D011948:Receptors, Antigen, T-Cell; D000099192:CD69 Antigens