Apoptotic Vesicles Crossprime CD8 T Cells and Protect against Tuberculosis

CD8 T lymphocytes are important effectors in protective immunity against Mycobacterium tuberculosis. We recently characterized the detour pathway of CD8 T cell activation in tuberculosis mediated by apoptotic vesicles from infected cells that transport mycobacterial antigens to dendritic cells (DCs)...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2006, Vol.24 (1), p.105-117
Main Authors: Winau, Florian, Weber, Stephan, Sad, Subash, de Diego, Juana, Hoops, Silvia Locatelli, Breiden, Bernadette, Sandhoff, Konrad, Brinkmann, Volker, Kaufmann, Stefan H.E., Schaible, Ulrich E.
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - therapeutic use
Animals
Apoptosis
BCG Vaccine - immunology
BCG Vaccine - therapeutic use
CD8-Positive T-Lymphocytes - immunology
Cell division
Cross-Priming - immunology
Dendritic Cells - immunology
Endosomes - immunology
Endosomes - metabolism
Endosomes - microbiology
Lymphocytes
Macrophages - microbiology
Macrophages - ultrastructure
Mice
Mycobacterium bovis - immunology
Mycobacterium tuberculosis
Saposins - metabolism
Scanning electron microscopy
Toll-Like Receptors - immunology
Tuberculosis
Tuberculosis - immunology
Tuberculosis - prevention & control
Vaccination - methods
Viral infections
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Summary:CD8 T lymphocytes are important effectors in protective immunity against Mycobacterium tuberculosis. We recently characterized the detour pathway of CD8 T cell activation in tuberculosis mediated by apoptotic vesicles from infected cells that transport mycobacterial antigens to dendritic cells (DCs). Here we demonstrate that apoptotic vesicles from mycobacteria-infected macrophages stimulate CD8 T cells in vivo. Homing of DCs to draining lymph nodes was critically required for effective crosspriming. Subsequent fate of vesicle-associated antigens in recipient DCs was characterized by endosomal mechanisms predominating over proteasomal processing. In addition, vesicle processing depended on the presence of saposins to disintegrate apoptotic membranes. Apoptotic vesicles displayed potent adjuvant activity by stimulating through Toll-like receptors (TLR). Ultimately, vaccination with vesicles from infected cells induced protection against M. tuberculosis infection. Taken together, we propose the detour pathway to represent a genuine immunological mechanism mediating crosspriming of CD8 T cells in vivo and protection against tuberculosis.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2005.12.001