Effect of activated antigen-specific B cells on ES-62-mediated modulation of effector function of heterologous antigen-specific T cells in vivo.
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.
Marshall
Fraser A
FA
Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, UK.
Watson
Katherine A
KA
Garside
Paul
P
Harnett
Margaret M
MM
Harnett
William
W
D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015801:Helminth Proteins / Q000276:immunology*; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
C435884:ES-62 protein, Acanthocheilonema viteae; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D015801:Helminth Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010047:Ovalbumin