A Schistosome-Expressed Immunomodulatory Glycoconjugate Expands Peritoneal Gr1 super(+) Macrophages That Suppress Naive CD4 super(+) T Cell Proliferation Via an IFN- gamma and Nitric Oxide-Dependent Mechanism

Lacto-N-fucopentaose III (LNFPIII) is found in human milk and on the Th2 driving helminth parasite Schistosoma mansoni. This pentasaccharide drives Th2-type responses in vivo and in vitro when conjugated to a carrier. In an attempt to further understand early events in Th1 to Th2 switching, we exami...

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Published in:The Journal of immunology (1950) 2001-10, Vol.167 (8), p.4293-4302
Main Authors: Atochina, O, Daly-Engel, T, Piskorska, D, McGuire, E, Harn, DA
Format: Article
Language:English
Subjects:
g-Interferon
glycoconjugates
Lacto-N-fucopentaose III
Schistosoma mansoni
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container_issue 8
container_start_page 4293
container_title The Journal of immunology (1950)
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creator Atochina, O
Daly-Engel, T
Piskorska, D
McGuire, E
Harn, DA
description Lacto-N-fucopentaose III (LNFPIII) is found in human milk and on the Th2 driving helminth parasite Schistosoma mansoni. This pentasaccharide drives Th2-type responses in vivo and in vitro when conjugated to a carrier. In an attempt to further understand early events in Th1 to Th2 switching, we examined phenotypic and functional changes in peritoneal cell populations in BALB/c and SCID mice following LNFPIII-dextran injection. We found that i.p. injection with LNFPIII-dextran resulted in rapid (
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This pentasaccharide drives Th2-type responses in vivo and in vitro when conjugated to a carrier. In an attempt to further understand early events in Th1 to Th2 switching, we examined phenotypic and functional changes in peritoneal cell populations in BALB/c and SCID mice following LNFPIII-dextran injection. We found that i.p. injection with LNFPIII-dextran resulted in rapid (&lt;20 h) expansion of the Gr1 super(+) subpopulation of F4/80 super(+)/CD11b super(+) peritoneal cells, comprising up to 75% of F4/80 super(+)/CD11b super(+) peritoneal cells compared with 18% in uninjected or dextran-injected mice. Functionally, these cells suppressed anti-CD3- and anti-CD28-induced proliferation of naive CD4 super(+) T cells. LNFPIII-dextran also expanded functional Gr1 super(+) suppressor macrophages in SCID mice, demonstrating that expansion and function of suppressor cells did not require T cells. Suppression in both BALB/c and SCID mice was NO and IFN- gamma dependent, as addition of inhibitors of inducible NO synthase (N super(G)-monomethyl-L-arginine), as well as anti-IFN- gamma Abs, restored the ability of CD4 super(+) T cells to proliferate in vitro. Depletion of the F4/80 super(+) subset of Gr1 super(+) cells eliminated the suppressive activity of peritoneal exudate cells showing that these cells were macrophages. Thus, LNFPIII-dextran rapidly expands the Gr1 super(+) suppressor macrophage population in the peritoneal cavities of otherwise naive mice. 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subjects g-Interferon
glycoconjugates
Lacto-N-fucopentaose III
Schistosoma mansoni
title A Schistosome-Expressed Immunomodulatory Glycoconjugate Expands Peritoneal Gr1 super(+) Macrophages That Suppress Naive CD4 super(+) T Cell Proliferation Via an IFN- gamma and Nitric Oxide-Dependent Mechanism
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