title: ES-62, an immunomodulator secreted by filarial nematodes, suppresses clonal expansion and modifies effector function of heterologous antigen-specific T cells in vivo.
abstract: ES-62 is a phosphorylcholine-containing glycoprotein secreted by filarial nematodes, which has previously been shown to possess a range of immunomodulatory capabilities. We now show, using a CD4+ transgenic TCR T cell adoptive transfer system, that ES-62 can modulate heterologous Ag (OVA)-specific responses in vivo. Thus, in contrast to the mixed IgG1-IgG2a response observed in control animals, ES-62-treated mice exhibited a Th2-biased IgG Ab response as evidenced by stable enhancement of anti-OVA IgG1 production and a profound inhibition of anti-OVA IgG2a. Consistent with this, Ag-specific IFN-gamma produced was suppressed by pre-exposure to ES-62 when T cells were rechallenged ex vivo. However, the response observed was not classical Th2, because although Ag-specific IL-5 production was enhanced by pre-exposure to ES-62, IL-13, and IL-4 were inhibited when T cells were rechallenged ex vivo. Moreover, such T cells produced lower levels of IL-2 and proliferated less upon Ag rechallenge ex vivo. Finally, pre-exposure to ES-62 inhibited the clonal expansion of the transferred Ag-specific CD4+ T cells and altered the functional response of such T cells in vivo, by modulating the kinetics and reducing the extent of their migration into B cell follicles.
authors.affiliation: Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Fraser A
authors.initials: FA
authors.lastname: Marshall
authors.forename: Angela M
authors.initials: AM
authors.lastname: Grierson
authors.forename: Paul
authors.initials: P
authors.lastname: Garside
authors.forename: William
authors.initials: W
authors.lastname: Harnett
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Harnett
mesh_terms: D000818:Animals; D015801:Helminth Proteins / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: C435884:ES-62 protein, Acanthocheilonema viteae; D015801:Helminth Proteins; D007074:Immunoglobulin G; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin