Direct stimulation of T cells by membrane vesicles from antigen-presenting cells

doi:10.1073/pnas.0603466103

Direct stimulation of T cells by membrane vesicles from antigen-presenting cells

*The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037;
^†Department of Immunology, Institute of Microbiology, Videnska 1083, 142 20 Prague 4, Czech Republic;
^‡Pharmexa–Epimmune Inc., 5820 Nancy Ridge Drive, San Diego, CA 92121; and
^§Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst NSW 2010, Australia

Edited by Jacques F. A. P. Miller, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia, and approved June 6, 2006 (received for review April 27, 2006)

Abstract

Activation of naïve T cells generally requires T cell receptor-mediated contact with MHC-bound peptides on viable antigen-presenting cells such as dendritic cells (DC). Here evidence is presented that dissociated cell membrane fragments from a DC line can be used as an effective substitute for viable DC. Ultracentrifuged material derived from sonicates of IFN-γ-matured DC is enriched in small membrane vesicles that closely resemble exosomes. When complexed with MHC class I-restricted specific peptide, vesicles from DC sonicates generate strong responses by purified naïve CD8⁺ cells in vitro in the absence of normal antigen-presenting cells and can also efficiently prime T cells for tumor rejection in vivo. Both in terms of total yields from DC and relative immunogenicity, membrane vesicles from DC sonicates are much more effective than classic exosomes and may be a valuable tool for tumor immunotherapy.

Footnotes

^¶To whom correspondence should be addressed. E-mail: j.sprent{at}garvan.org.au
Author contributions: M.K., O.B., X.S., I.H., R.K., and J.S. designed research; M.K., O.B., and R.K. performed research; M.K. and J.S. analyzed data; and M.K., R.K., and J.S. wrote the paper.
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

TCR,

T cell receptor;

APC,

antigen-presenting cell;

DC,

dendritic cell;

LN,

lymph node;

CFSE,

carboxyfluorescein succinimidyl ester.