Pathogenic organisms such as bacteria, viruses and parasitic worms have evolved strategies to actively subvert the host immune system, facilitating their persistence. As a consequence, the identification of specific pathogen derived immunomodulatory molecules has become an intense area of research with a number of such molecules having been found to offer potential as immunotherapeutics in animal models of autoimmune disease and allergy. As there is considerable overlap between the cellular immune responses mounted against 'self' antigens in the case of autoimmunity, and alloantigens in the context of transplantation, we will examine whether immunomodulatory components identified from the excretory secretory (ES) products of the helminth parasite, Fasciola hepatica can alter the generation of an alloimmune response. We will examine the influence of specific immunomodulatory ES components on the generation of alloresponses by examining their specific effects on both antigen presenting cells and T cells. Furthermore we will examine the efficacy of specific ES products in promoting transplant tolerance in models of graft versus host disease and organ transplantation.
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