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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).

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