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ES-62, an Immunomodulator Secreted by Filarial Nematodes, Suppresses Clonal Expansion and Modifies Effector Function of Heterologous Antigen-Specific T Cells In Vivo¹

Fraser A. Marshall^*, Angela M. Grierson^*, Paul Garside^*, William Harnett and Margaret M. Harnett^2,*

^* Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom; and Department of Immunology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom

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- 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.

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