Peripheral host T cells survive hematopoietic stem cell transplantation and promote graft-versus-host disease

Divito, Sherrie J.; Aasebo, Anders T.; Matos, Tiago R.; Hsieh, Pei‐Chen; Collin, Matthew; Elco, Christopher P.; O’Malley, John T.; Bækkevold, Espen S.; Reims, Henrik M.; Gedde‐Dahl, Tobias; Hagerstrom, Michael; Hilaire, Jude; Lian, John; Milford, Edgar L.; Pinkus, Geraldine S.; Ho, Vincent T.; Soiffer, Robert J.; Kim, Haesook T.; Mihm, Martín C.; Ritz, Jérôme; Guleria, Indira; Cutler, Corey; Clark, Rachael A.; Jahnsen, Frode L.; Kupper, Thomas S.

doi:10.1172/jci129965

Cited by 64 publications

(78 citation statements)

References 52 publications

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“…As described in the accompanying manuscript by Divito et al ( 51 ), host tissues affected by GVHD, such as the skin and gut, contain a notable proportion of host-resident T cells that survive for many months and are found in an activated state in association with donor macrophages. Our results support the conclusion that donor-derived macrophages have enhanced antigen-presenting functions that could enable the activation of residual host T cells, resulting in host-versus-graft responses that may be indistinguishable from GVHD clinically.…”

Section: Discussionmentioning

confidence: 99%

“…We have shown that donor macrophages are capable of performing both antigen-presenting and cytotoxic functions, but these may also be differentially involved depending on whether inflammation is primarily driven by recipient or donor T cells. Divito et al observe that skin and gut both have prominent populations of resident T cells, and it will be important to explore the potential of donor macrophages to activate host T cells in gut GVHD ( 51 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Donor monocyte–derived macrophages promote human acute graft-versus-host disease

Jardine¹,

Cytlak²,

Gunawan³

et al. 2020

Journal of Clinical Investigation

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Donor monocyte–derived macrophages promote human acute graft-versus-host disease

Jardine¹,

Cytlak²,

Gunawan³

et al. 2020

Journal of Clinical Investigation

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“…Clinical observations suggest that skin-resident T cells survive "lymphocyte-depleting" chemotherapy, as patients who are profoundly lymphopenic following chemotherapy can still develop T cell-mediated drug rashes despite the absence of circulating lymphocytes [21]. In agreement with these observations Divito et al [22], showed that host T cells survive conditioning prior to allo-HSCT and are present in target tissues during aGVHD. The study showed a proinflammatory role for host T cells in peripheral tissues.…”

Section: Acute Gvhdmentioning

confidence: 81%

Acute Graft-Versus-Host Disease, Prophylaxis and Therapy

Sharma¹,

Efebera²

2021

OBM Transplantation

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Graft-versus host disease is one of the major causes of death in patients undergoing allogeneic hematopoietic stem cell transplantation. Major contributing factors to severity of graft-versus host disease include HLA mismatch, conditioning regimen intensity, age of donor and recipient, source of stem cell, and donor type. Strategies and clinical trials are ongoing to reduce the incidence of graft-versus host disease, and to improve on the survival outcome of patients with graft-versus host disease, Research efforts continue to develop new ways of identification, prevention, and treatment for graft versus host disease. In addition, efforts are also being made to incorporate biomarker for the early detection of graft versus host disease. In addition, strategies utilizing monoclonal antibodies and cytokines are being tested as potential therapeutic options. Here we provide evidence for recommended regimens for graft versus host disease, prophylaxis and treatment.

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“…These results can be used to guide clinical decisions to prevent or treat acute GVHD [ 78 ]. By analyzing skin and peripheral blood T cells using TCR-seq, host skin-resident T cells were found to have an unanticipatedly pathogenic impact on GVHD [ 107 ].…”

Section: Applications Of Scrna-seq For Transplantationmentioning

confidence: 99%

Advances in single-cell sequencing: insights from organ transplantation

Wang

Schnieke

et al. 2021

Military Med Res

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Single-cell RNA sequencing (scRNA-seq) is a comprehensive technical tool to analyze intracellular and intercellular interaction data by whole transcriptional profile analysis. Here, we describe the application in biomedical research, focusing on the immune system during organ transplantation and rejection. Unlike conventional transcriptome analysis, this method provides a full map of multiple cell populations in one specific tissue and presents a dynamic and transient unbiased method to explore the progression of allograft dysfunction, starting from the stress response to final graft failure. This promising sequencing technology remarkably improves individualized organ rejection treatment by identifying decisive cellular subgroups and cell-specific interactions.

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Peripheral host T cells survive hematopoietic stem cell transplantation and promote graft-versus-host disease

Cited by 64 publications

References 52 publications

Donor monocyte–derived macrophages promote human acute graft-versus-host disease

Donor monocyte–derived macrophages promote human acute graft-versus-host disease

Acute Graft-Versus-Host Disease, Prophylaxis and Therapy

Advances in single-cell sequencing: insights from organ transplantation

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