Published online before print July 11, 2007

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: jlb.0407249v1 82/4/829    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hao, S. Articles by Xiang, J. Search for Related Content PubMed PubMed Citation Articles by Hao, S. Articles by Xiang, J.

(Journal of Leukocyte Biology. 2007;82:829-838.)
© 2007 by Society for Leukocyte Biology

Nonspecific CD4⁺ T cells with uptake of antigen-specific dendritic cell-released exosomes stimulate antigen-specific CD8⁺ CTL responses and long-term T cell memory

Research Unit, Division of Health Research, Saskatchewan Cancer Agency, Departments of Oncology, Microbiology and Immunology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

¹ Correspondence: Saskatoon Cancer Center, 20 Campus Drive, Saskatoon, SK S7N 4H4, Canada. E-mail: jxiang{at}scf.sk.ca

ABSTRACT

Dendritic cell (DC) and DC-derived exosomes (EXO) have been used extensively for tumor vaccination. However, its therapeutic efficiency is limited to only production of prophylactic immunity against tumors. T cells can uptake DC-released EXO. However, the functional effect of transferred exosomal molecules on T cells is unclear. In this study, we demonstrated that OVA protein-pulsed DC-derived EXO (EXO_OVA) can be taken up by Con A-stimulated, nonspecific CD4⁺ T cells derived from wild-type C57BL/6 mice. The active EXO-uptaken CD4⁺ T cells (aT_EXO), expressing acquired exosomal MHC I/OVA I peptide (pMHC I) complexes and costimulatory CD40 and CD80 molecules, can act as APCs capable of stimulating OVA-specific CD8⁺ T cell proliferation in vitro and in vivo and inducing efficient CD4⁺ Th cell-independent CD8⁺ CTL responses in vivo. The EXO_OVA-uptaken CD4⁺ aT_EXO cell vaccine induces much more efficient CD8⁺ T cell responses and immunity against challenge of OVA-transfected BL6-10 melanoma cells expressing OVA in wild-type C57BL/6 mice than EXO_OVA. The in vivo stimulatory effect of the CD4⁺ aT_EXO cell to CD8⁺ T cell responses is mediated and targeted by its CD40 ligand signaling/acquired exosomal CD80 and pMHC I complexes, respectively. In addition, CD4⁺ aT_EXO vaccine stimulates a long-term, OVA-specific CD8⁺ T cell memory. Therefore, the EXO_OVA-uptaken CD4⁺ T cells may represent a new, effective, EXO-based vaccine strategy in induction of immune responses against tumors and other infectious diseases.

Key Words: aT_EXO • pMHC I • T cell vaccine • antitumor immunity

This article has been cited by other articles:

				X. Zhang, M. A. Munegowda, J. Yuan, Y. Wei, and J. Xiang Optimal TLR9 signal converts tolerogenic CD4-8- DCs into immunogenic ones capable of stimulating antitumor immunity via activating CD4+ Th1/Th17 and NK cell responses J. Leukoc. Biol., August 1, 2010; 88(2): 393 - 403. [Abstract] [Full Text] [PDF]

				K. R. Qazi, U. Gehrmann, E. Domange Jordo, M. C. I. Karlsson, and S. Gabrielsson Antigen-loaded exosomes alone induce Th1-type memory through a B cell-dependent mechanism Blood, March 19, 2009; 113(12): 2673 - 2683. [Abstract] [Full Text] [PDF]