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

Publisher Website
Google Scholar
Abstract
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 (<20 h) expansion of the Gr1+ subpopulation of F4/80+/CD11b+ peritoneal cells, comprising up to 75% of F4/80+/CD11b+ 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+ T cells. LNFPIII-dextran also expanded functional Gr1+ 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-γ dependent, as addition of inhibitors of inducible NO synthase (NG-monomethyl-l-arginine), as well as anti-IFN-γ Abs, restored the ability of CD4+ T cells to proliferate in vitro. Depletion of the F4/80+ subset of Gr1+ cells eliminated the suppressive activity of peritoneal exudate cells showing that these cells were macrophages. Thus, LNFPIII-dextran rapidly expands the Gr1+ suppressor macrophage population in the peritoneal cavities of otherwise naive mice. These Gr1+ cells suppress proliferation of naive CD4+ T cells in an NO-dependent mechanism, and may play a regulatory role in the switching of Th1- to Th2-type responses.
Keywords

This publication has 49 references indexed in Scilit: