After Bone Marrow Transplantation, the Cell-Intrinsic Th2 Pathway Promotes Recipient T Lymphocyte Survival and Regulates Graft-versus-Host Disease.

Recipient T cells can aggravate or regulate lethal and devastating graft-versus-host disease (GVHD) after bone marrow transplantation (BMT). In this context, we have shown before that intestinal immune conditioning with helminths is associated with survival of recipient T cells and Th2 pathway-dependent regulation of GVHD. We investigated the mechanism of survival of recipient T cells and their contribution to GVHD pathogenesis in this helminth infection and BMT model after myeloablative preparation with total body irradiation in mice. Our results indicate that the helminth-induced Th2 pathway directly promotes the survival of recipient T cells after total body irradiation. Th2 cells also directly stimulate recipient T cells to produce TGF-ß, which is required to regulate donor T cell-mediated immune attack of GVHD and can thereby contribute to recipient T cell survival after BMT. Moreover, we show that recipient T cells, conditioned to produce Th2 cytokines and TGF-ß after helminth infection, are fundamentally necessary for GVHD regulation. Taken together, reprogrammed or immune-conditioned recipient T cells after helminth infection are crucial elements of Th2- and TGF-ß-dependent regulation of GVHD after BMT, and their survival is dependent on cell-intrinsic Th2 signaling.

Helminth Lessons in Inflammatory Bowel Diseases (IBD).

Helminths are multicellular invertebrates that colonize the gut of many vertebrate animals including humans. This colonization can result in pathology, which requires treatment. It can also lead to a commensal and possibly even a symbiotic relationship where the helminth and the host benefit from each other's presence. Epidemiological data have linked helminth exposure to protection from immune disorders that include a wide range of diseases, such as allergies, autoimmune illnesses, and idiopathic inflammatory disorders of the gut, which are grouped as inflammatory bowel diseases (IBD). Treatment of moderate to severe IBD involves the use of immune modulators and biologics, which can cause life-threatening complications. In this setting, their safety profile makes helminths or helminth products attractive as novel therapeutic approaches to treat IBD or other immune disorders. Helminths stimulate T helper-2 (Th2) and immune regulatory pathways, which are targeted in IBD treatment. Epidemiological explorations, basic science studies, and clinical research on helminths can lead to the development of safe, potent, and novel therapeutic approaches to prevent or treat IBD in addition to other immune disorders.