Apoptotic vesicles crossprime CD8 T cells and protect against tuberculosis.

Winau, F; Weber, S; Sad, S; de Diego, J; Hoops, SL; Breiden, B; Sandhoff, K; Brinkmann, V; Kaufmann, SH; Schaible, UE; (2006) Apoptotic vesicles crossprime CD8 T cells and protect against tuberculosis. Immunity, 24 (1). pp. 105-17. ISSN 1074-7613 DOI: https://doi.org/10.1016/j.immuni.2005.12.001

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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.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: TB Centre
PubMed ID: 16413927
Web of Science ID: 234850200014
URI: http://researchonline.lshtm.ac.uk/id/eprint/11259


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