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Blood, 15 November 2000, Vol. 96, No. 10, pp. 3505-3513

IMMUNOBIOLOGY

Presentation of proteins encapsulated in sterically stabilized liposomes by dendritic cells initiates CD8+ T-cell responses in vivo

Ralf Ignatius, Karsten Mahnke, Miguel Rivera, Keelung Hong, Frank Isdell, Ralph M. Steinman, Melissa Pope, and Leonidas Stamatatos

From the Laboratory of Cellular Physiology and Immunology and the Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY; and the California Pacific Medical Center Research Institute, San Francisco, CA.

Liposomes have been proposed as a vehicle to deliver proteins to antigen-presenting cells (APC), such as dendritic cells (DC), to stimulate strong T cell-mediated immune responses. Unfortunately, because of their instability in vivo and their rapid uptake by cells of the mononuclear phagocyte system on intravenous administration, most types of conventional liposomes lack clinical applicability. In contrast, sterically stabilized liposomes (SL) have increased in vivo stability. It is shown that both immature and mature DC take up SL into neutral or mildly acidic compartments distinct from endocytic vacuoles. These DC presented SL-encapsulated protein to both CD4+ and CD8+ T cells in vitro. Although CD4+ T-cell responses were comparable to those induced by soluble protein, CD8+ T-cell proliferation was up to 300-fold stronger when DC had been pulsed with SL-encapsulated ovalbumin. DC processed SL-encapsulated antigen through a TAP-dependent mechanism. Immunization of mice with SL-encapsulated ovalbumin led to antigen presentation by DC in vivo and stimulated greater CD8+ T-cell responses than immunization with soluble protein or with conventional or positively charged liposomes carrying ovalbumin. Therefore, the application of SL-encapsulated antigens offers a novel effective, safe vaccine approach if a combination of CD8+ and CD4+ T-cell responses is desired (ie, in anti-viral or anti-tumor immunity).

© 2000 by The American Society of Hematology.
 

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