Adult Bone Marrow Transplant Service, Division of Hematologic Malignancies, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, and The Rockefeller University, New York, New York, USA.
Address correspondence to: James W. Young, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Zuckerman 704, New York, New York 10065, USA. Phone: 646.888.2052; Email: firstname.lastname@example.org.
First published July 27, 2020 - More info
Allogeneic hematopoietic cell transplantation (alloHCT) benefits increasing numbers of patients with otherwise lethal diseases. Graft-versus-host disease (GVHD), however, remains one of the most potentially life-threatening complications due to its own comorbidities and the side effects of its treatment. In this issue of the JCI, two groups have turned dogma on its head by providing evidence for alternative mechanisms of acute GVHD (aGVHD) in humans. The principle of donor T cell reactivity elicited by host antigen-presenting cells (APCs) expressing MHC-encoded major HLA disparities or expressing minor histocompatibility antigen (miHA) differences presented by identical HLA molecules remains intact. These reports, however, demonstrate that GVHD can additionally result from peripheral host T cells resident in skin and gut being stimulated against donor APCs in the form of monocyte-derived macrophages. Moreover, these donor monocyte-derived macrophages can themselves mediate cytopathic effects against resident host T cells in skin explants and against a keratinocyte-derived cell line.
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