HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Krishnan, L. Articles by Sprott, G. D. Search for Related Content PubMed PubMed Citation Articles by Krishnan, L. Articles by Sprott, G. D.

Archaeosomes Induce Long-Term CD8⁺ Cytotoxic T Cell Response to Entrapped Soluble Protein by the Exogenous Cytosolic Pathway, in the Absence of CD4⁺ T Cell Help¹

Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada

The unique ether glycerolipids of Archaea can be formulated into vesicles (archaeosomes) with strong adjuvant activity for MHC class II presentation. Herein, we assess the ability of archaeosomes to facilitate MHC class I presentation of entrapped protein Ag. Immunization of mice with OVA entrapped in archaeosomes resulted in a potent Ag-specific CD8⁺ T cell response, as measured by IFN- production and cytolytic activity toward the immunodominant CTL epitope OVA_257–264. In contrast, administration of OVA with aluminum hydroxide or entrapped in conventional ester-phospholipid liposomes failed to evoke significant CTL response. The archaeosome-mediated CD8⁺ T cell response was primarily perforin dependent because CTL activity was undetectable in perforin-deficient mice. Interestingly, a long-term CTL response was generated with a low Ag dose even in CD4⁺ T cell deficient mice, indicating that the archaeosomes could mediate a potent T helper cell-independent CD8⁺ T cell response. Macrophages incubated in vitro with OVA archaeosomes strongly stimulated cytokine production by OVA-specific CD8⁺ T cells, indicating that archaeosomes efficiently delivered entrapped protein for MHC class I presentation. This processing of Ag was Brefeldin A sensitive, suggesting that the peptides were transported through the endoplasmic reticulum and presented by the cytosolic MHC class I pathway. Finally, archaeosomes induced a potent memory CTL response to OVA even 154 days after immunization. This correlated to strong Ag-specific up-regulation of CD44 on splenic CD8⁺ T cells. Thus, delivery of proteins in self-adjuvanting archaeosomes represents a novel strategy for targeting exogenous Ags to the MHC class I pathway for induction of CTL response.

This article has been cited by other articles:

				G D. Sprott, C. J Dicaire, J.-P. Cote, and D. M Whitfield Adjuvant potential of archaeal synthetic glycolipid mimetics critically depends on the glyco head group structure Glycobiology, July 1, 2008; 18(7): 559 - 565. [Abstract] [Full Text] [PDF]

				P. H. Horne, M. A. Koester, K. Jayashankar, K. E. Lunsford, H. L. Dziema, and G. L. Bumgardner Disparate Primary and Secondary Allospecific CD8+ T Cell Cytolytic Effector Function in the Presence or Absence of Host CD4+ T Cells J. Immunol., July 1, 2007; 179(1): 80 - 88. [Abstract] [Full Text] [PDF]

				L. Krishnan, K. Gurnani, C. J. Dicaire, H. van Faassen, A. Zafer, C. J. Kirschning, S. Sad, and G. D. Sprott Rapid Clonal Expansion and Prolonged Maintenance of Memory CD8+ T Cells of the Effector (CD44highCD62Llow) and Central (CD44highCD62Lhigh) Phenotype by an Archaeosome Adjuvant Independent of TLR2 J. Immunol., February 15, 2007; 178(4): 2396 - 2406. [Abstract] [Full Text] [PDF]

				I. Rosenkrands, E. M. Agger, A. W. Olsen, K. S. Korsholm, C. S. Andersen, K. T. Jensen, and P. Andersen Cationic Liposomes Containing Mycobacterial Lipids: a New Powerful Th1 Adjuvant System Infect. Immun., September 1, 2005; 73(9): 5817 - 5826. [Abstract] [Full Text] [PDF]

				G. D. Sprott, C. J. Dicaire, K. Gurnani, S. Sad, and L. Krishnan Activation of Dendritic Cells by Liposomes Prepared from Phosphatidylinositol Mannosides from Mycobacterium bovis Bacillus Calmette-Guerin and Adjuvant Activity In Vivo Infect. Immun., September 1, 2004; 72(9): 5235 - 5246. [Abstract] [Full Text] [PDF]

				K. Gurnani, J. Kennedy, S. Sad, G. D. Sprott, and L. Krishnan Phosphatidylserine Receptor-Mediated Recognition of Archaeosome Adjuvant Promotes Endocytosis and MHC Class I Cross-Presentation of the Entrapped Antigen by Phagosome-to-Cytosol Transport and Classical Processing J. Immunol., July 1, 2004; 173(1): 566 - 578. [Abstract] [Full Text] [PDF]

				L. Krishnan, S. Sad, G. B. Patel, and G. D. Sprott Archaeosomes Induce Enhanced Cytotoxic T Lymphocyte Responses to Entrapped Soluble Protein in the Absence of Interleukin 12 and Protect against Tumor Challenge Cancer Res., May 15, 2003; 63(10): 2526 - 2534. [Abstract] [Full Text] [PDF]

				R. Dudani, Y. Chapdelaine, H. van Faassen, D. K. Smith, H. Shen, L. Krishnan, and S. Sad Preexisting Inflammation Due to Mycobacterium bovis BCG Infection Differentially Modulates T-Cell Priming against a Replicating or Nonreplicating Immunogen Infect. Immun., April 1, 2002; 70(4): 1957 - 1964. [Abstract] [Full Text] [PDF]

				L. Krishnan, S. Sad, G. B. Patel, and G. D. Sprott The Potent Adjuvant Activity of Archaeosomes Correlates to the Recruitment and Activation of Macrophages and Dendritic Cells In Vivo J. Immunol., February 1, 2001; 166(3): 1885 - 1893. [Abstract] [Full Text] [PDF]