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Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada
The unique glycerolipids of Archaea can be
formulated into vesicles (archaeosomes) with potent adjuvant activity.
We studied the effect of archaeosomes on APCs to elucidate the
mechanism(s) of adjuvant action. Exposure of J774A.1 macrophages to
archaeosomes in vitro resulted in up-regulation of B7.1, B7.2, and MHC
class II molecules to an extent comparable to that achieved with LPS.
Similarly, incubation of bone marrow-derived DCs with archaeosomes
resulted in enhanced expression of MHC class II and B7.2 molecules. In
contrast, conventional liposomes made from ester phospholipids failed
to modulate the expression of these activation markers. APCs treated
with archaeosomes exhibited increased TNF production and functional
ability to stimulate allogenic T cell proliferation. More
interestingly, archaeosomes enhanced APC recruitment and activation in
vivo. Intraperitoneal injection of archaeosomes into mice led to
recruitment of Mac1
+, F4/80+ and
CD11c+ cells. The expression of MHC class II on the surface
of peritoneal cells was also enhanced. Furthermore, peritoneal cells
from archaeosome-injected mice strongly enhanced allo-T cell
proliferation and cytokine production. The ability of
archaeosome-treated APCs to stimulate T cells was restricted to
Mac1high, B220- cells in the peritoneum.
These Mac1high cells in the presence of GM-CSF gave rise
to both F4/80+ (macrophage) and CD11c+
(dendritic) populations. Overall, the activation of APCs correlated to
the ability of archaeosomes to induce strong humoral, T helper, and CTL
responses to entrapped Ag. Thus, the recruitment and activation of
professional APCs by archaeosomes constitutes an efficient
self-adjuvanting process for induction of Ag-specific responses to
encapsulated Ags.
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