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

Liposomes have been proposed as a vehicle to deliver proteins to antigen-pr esenting cells (APC), such as dendritic cells (DC), to stimulate strong T c ell-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 c linical applicability. In contrast, sterically stabilized liposomes (SL) ha ve increased in vivo stability. It is shown that both immature and mature D C take up SL into neutral or mildly acidic compartments distinct from endoc ytic vacuoles, These DC presented SL-encapsulated protein to both CD4(+) an d 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. Imm unization of mice with SL-encapsulated ovalbumin led to antigen presentatio n by DC in vivo and stimulated greater CD8(+) T-cell responses than immuniz ation with soluble protein or with conventional or positively charged lipos omes carrying ovalbumin, Therefore, the application of SL-encapsulated anti gens offers a novel effective, safe vaccine approach if a combination of CD 8(+) and CD4(+) T-cell responses is desired tie, in anti-viral or anti-tumo r immunity), (C) 2000 by The American Society of Hematology.