2014 - Chris Johnson

The role of helminth parasites in achieving immunological tolerance

Introduction: Helminth worms currently infect more than one quarter of the world’s population and their success as parasites owes much to active immunomodulation of the host immune response. This project sets out to determine whether helminth infection reduces the immune response to allograft transplantation and how this may become therapeutically tractable.

Methods: Under Home Office licence C57BL/6 mice were implanted with a subcutaneous minipump delivering a continuous infusion of secreted products from the intestinal parasite, Heligmosomoides polygyrus. Simultaneously, fully allogeneic skin grafts were performed from BALBc donors. Seven days later, lymphocytes were isolated from allograft draining lymph nodes and analysed by flow cytometry.

Results: Flow cytometric analysis reveals a 41.7% increase in the mean percentage of CD4⁺CD25⁺Foxp3⁺ regulatory T cells (of total CD4⁺ cells) in treated vs. untreated mice (p=0.0085). Treatment with parasite products also increased mean expression of the regulatory cell surface receptor PD-1, specifically in the effector CD4+ T cell population, by 62.2% (p=0.03).

Conclusions: Our results demonstrate that helminth-derived products can powerfully induce regulatory immunological mechanisms in the presence of a fully allogeneic transplant. Identification of the mechanisms involved in suppression of allograft rejection by helminth parasites may lead towards development of safe and effective novel therapeutic strategies.