Effect of activated antigen‐specific B cells on ES‐62‐mediated modulation of effector function of heterologous antigen‐specific T cells in vivo

Summary 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.