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ARS Home » Northeast Area » Beltsville, Maryland (BARC) » Beltsville Agricultural Research Center » Animal Parasitic Diseases Laboratory » Research » Publications at this Location » Publication #401748

Research Project: Molecular, Immune and Microbiome Approaches for Mitigating GI Nematode Infections of Livestock

Location: Animal Parasitic Diseases Laboratory

Title: After bone marrow transplantation, cell-intrinsic T Helper-2 (Th2) pathway promotes recipient T lymphocyte survival and regulates the graft-versus-host disease

item TRUSCOTT, J. - University Of Iowa
item GUAN, X. - University Of Iowa
item FURY, H. - University Of Iowa
item ATAGOZLI, T. - University Of Iowa
item METWALI, A. - University Of Iowa
item LIU, W. - University Of Iowa
item LI, Y. - University Of Iowa
item Urban, Joseph
item Li, Robert
item BROMBACHER, F. - University Of Cape Town
item ELLIOTT, D.E. - University Of Iowa
item BLAZER, B.R. - University Of Minnesota
item INCE, M.N. - University Of Iowa

Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/27/2023
Publication Date: 6/1/2023
Citation: Truscott, J., Guan, X., Fury, H., Atagozli, T., Metwali, A., Liu, W., Li, Y., Urban Jr, J.F., Li, R.W., Brombacher, F., Elliott, D., Blazer, B., Ince, M. 2023. After bone marrow transplantation, cell-intrinsic T Helper-2 (Th2) pathway promotes recipient T lymphocyte survival and regulates the graft-versus-host disease. Journal of Immunology.

Interpretive Summary: Graft-versus-host disease is a lethal and devastating complication of bone marrow transplantation (BMT), affecting half of BMT recipients and causing the organ damage. Innovative methods to promote transplantation tolerance are needed to ensure a successful transplantation and the survival of transplant recipients. In this study, ARS scientists and academic collaborators discovered that helminth parasite infection can promote transplant immunity and tolerance in animal models. Further, helminth infection constitutes a safe approach with no severe side effects in clinical practice. The findings demonstrate that studying natural responses to parasitic infections can simultaneously benefit animal and human health. For decades, ARS researchers have discovered that common veterinary parasites inform us about, and help manage, human disease and wellness.

Technical Abstract: 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 T helper-2 (Th2) pathway-dependent regulation of graft-versus-host disease (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 (TBI). Our results indicate that helminth-induced Th2 pathway directly promotes the survival of recipient T cells after TBI. Th2 cells also directly stimulate recipient T cells to produce TGFß, 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' 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'-dependent regulation of GVHD after BMT and their survival is dependent on cell-intrinsic Th2 signaling.