One-two punch injury to tolerance mechanisms in graft-versus-host disease
Léolène J. Carrington1,2 and Ivan Maillard1,2
1Division of Hematology-Oncology, Department of Medicine, and
2Abramson Family Cancer Research Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Address correspondence to: Ivan Maillard, 421 Curie Boulevard, BRB-2/3 Room 451, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. Phone: 215.746.2929; Email: imaillar@pennmedicine.upenn.edu.
Find articles by Carrington, L. in: JCI | PubMed | Google Scholar
1Division of Hematology-Oncology, Department of Medicine, and
2Abramson Family Cancer Research Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Address correspondence to: Ivan Maillard, 421 Curie Boulevard, BRB-2/3 Room 451, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. Phone: 215.746.2929; Email: imaillar@pennmedicine.upenn.edu.
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First published March 9, 2020 - More info
J Clin Invest. 2020;130(4):1625–1628. https://doi.org/10.1172/JCI136139.
© 2020 American Society for Clinical Investigation
Chronic graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic cell transplantation that resembles autoimmunity, with unclear pathogenesis and few effective therapeutic options. In this issue of the JCI, Dertschnig et al. used mouse models to investigate the basis of T cell autoreactivity following GVHD. Notably, GVHD caused irreversible damage to a population of tolerogenic stromal cells that display peripheral tissue–restricted antigens in lymph nodes, which impaired their capacity to purge and suppress autoreactive T cells. Together with damage to central tolerance mechanisms in the thymus, these findings outline a critical one-two punch injury that profoundly disrupts immune tolerance in this devastating disease.
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