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*
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115; and
Neose Technologies Inc., Horsham, PA 19044
Immunomodulatory oligosaccharides found on helminths also are found
in human milk, and both helminths and milk have been shown to be
immunosuppressive. We have been examining the immunomodulatory
capabilities of two oligosaccharides expressed in milk and on helminth
parasites, lacto-N-fucopentaose III and
lacto-N-neotetraose (LNnT). In an attempt to dissect
mechanisms that lead to Th2 polarization and immune suppression, we
examined the early response in mice to the glycoconjugate LNnT-Dextran
(LNnT-Dex). We found that injection of LNnT-Dex expanded a cell
population, phenotypically defined as
Gr1+/CD11b+/F4/80+, as early as
2 h after injection. Examination of spontaneous cytokine
production showed that this Gr1+/F4/80+
population of cells spontaneously produced low levels of
proinflammatory cytokines, but higher levels of IL-10 and TGF-
ex
vivo, compared to peritoneal cells from mice injected with Dex.
Gr1+ cells adoptively suppressed naive CD4+ T
cell proliferation in vitro in response to anti-CD3/CD28 Ab
stimulation. Suppression of naive CD4+ cells involved cell
contact and was dependent on IFN-
and NO, with a discrete role
played by IL-10. Coculture of naive CD4+T cells with
Gr1+ suppressor cells did not lead to CD4+ T
cell apoptosis, although it did imprint on naive CD4+ T
cells a response characterized by lower levels of IFN-, coincident
with increased IL-13 production. Our results suggest that both human
milk and helminth parasites may share a ligand-specific mechanism
involved in the generation of anti-inflammatory mediators that suppress
Th1-type and inflammatory responses.
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