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., Watson, K. A., Garside, P. , 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. (doi:10.1111/j.1365-2567.2007.02706.x)

Marshall, F. A., Watson, K. A., Garside, P. , 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. (doi:10.1111/j.1365-2567.2007.02706.x)

Full text not currently available from Enlighten.

Publisher's URL: http://dx.doi.org/10.1111/j.1365-2567.2007.02706.x

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Harnett, Professor Margaret and Garside, Professor Paul
Authors: Marshall, F. A., Watson, K. A., Garside, P., Harnett, M. M., and Harnett, W.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Immunology
Publisher:Wiley-Blackwell Publishing
ISSN:0019-2805
ISSN (Online):1365-2567
Published Online:24 October 2007
Related URLs:

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
410691T cell signalling events in vivo during the induction of immunity and toleranceMargaret HarnettMedical Research Council (MRC)G0500580Infection Immunity and Inflammation Medicine
271791Dissection of the Cellular and Molecular Basis of Immunoregulation in VivoMargaret HarnettMedical Research Council (MRC)G9901386Infection Immunity and Inflammation Medicine