Effect of activated antigen-specific b cells on es-62-mediated modulation of effector function of heterologous antigen-specific t cells in vivo

Marshall, F.A. and Watson, K.A. and Garside, P. and Harnett, M.M. and Harnett, W. (2008) Effect of activated antigen-specific b cells on es-62-mediated modulation of effector function of heterologous antigen-specific t cells in vivo. Immunology, 123 (3). pp. 411-425. ISSN 0019-2805 (http://dx.doi.org/10.1111/j.1365-2567.2007.02706.x)

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Abstract

There is currently great interest in the idea of using helminth-derived molecules for therapeutic purposes and indeed we have shown that ES-62, a filarial nematode-derived phosphorylcholine-containing glycoprotein, significantly reduces the severity of arthritis in a murine model. Clearly, knowledge of mechanism of action is important when considering molecules for use in treating disease and although much is known regarding how ES-62 interacts with the immune system, gaps in our understanding remain. A feature of filarial nematode infection is a defective, T helper 2 (Th2)-polarized antigen-specific T-cell response and in relation to this we have recently shown that ES-62 inhibits clonal expansion and modulates effector function towards a Th2 phenotype, of antigen-specific T cells in vivo. ES-62 is also known to directly modulate B-cell behaviour and hence to determine whether it was mediating these effects on T cells by disrupting B-T-cell co-operation, we have investigated antigen-specific responses using an adoptive transfer system in which traceable numbers of tg ovalbumin (OVA)-specific T cells and hen egg lysozyme (HEL)-specific B cells respond to a chemically coupled form of OVA-HEL that contains linked epitopes that promote cognate T- and B-cell interactions. Surprisingly, these studies indicate that activated B cells restore T-cell expansion and prevent Th2-like polarization. However, ES-62-treated double cell transfer mice demonstrate a more generalized immunosuppression with reduced levels of Th1 and -2 type cytokines and antibody subclasses. Collectively, these results suggest that whilst ES-62 can target B-T-cell co-operation, this does not promote polarizing of T-cell responses towards a Th2-type phenotype.

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