Apoptotic vesicles crossprime CD8 T cells and protect against tuberculosis

被引：325

作者：

Winau, F

Weber, S

Sad, S

de Diego, J

Hoops, SL

Breiden, B

Sandhoff, K

Brinkmann, V

Kaufmann, SHE

Schaible, UE

机构：

[1] Max Planck Inst Infect Biol, Dept Immunol, D-10117 Berlin, Germany

[2] Max Planck Inst Infect Biol, Dept Cellular Microbiol, D-10117 Berlin, Germany

[3] Max Planck Inst Infect Biol, Cent Core Facil Microscopy, D-10117 Berlin, Germany

[4] Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada

[5] Kekule Inst Organ Chem & Biochem, D-53121 Bonn, Germany

来源：

IMMUNITY | 2006年 / 24卷 / 01期

关键词：

D O I：

10.1016/j.immuni.2005.12.001

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：105 / 117

页数：13

共 54 条

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