Journal
SCIENCE IMMUNOLOGY
Volume 7, Issue 67, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciimmunol.abe2634
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Funding
- Deutsche Forschungsgemeinschaft [210592381, 360372040, 210879364, TRR/SFB 124, SFB 1054, SFB 1335]
- Deutsche Forschungsgemeinschaft (Excellence Cluster Balance of the Microverse)
- German Center of Infection Research (DZIF)
- German Federal Ministry of Research (BMBF) [LPI-BT1]
- Carl-Zeiss Stiftung
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Tissue-resident memory T cells (T-RM) play crucial roles in host defense in various tissues and barrier sites. However, the maintenance and regulatory checkpoints of human T-RM cells are still poorly understood. A study on patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) revealed long-term sequestration of host T cells in human skin. This finding sheds light on the characteristics and functions of skin-resident T-RM cells in humans.
Tissue-resident memory T cells (T-RM) have recently emerged as crucial cellular players for host defense in a wide variety of tissues and barrier sites. Insights into the maintenance and regulatory checkpoints of human T-RM cells remain scarce, especially due to the difficulties associated with tracking T cells through time and space in humans. We therefore sought to identify and characterize skin-resident T cells in humans defined by their long-term in situ lodgment. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) preceded by myeloablative chemotherapy unmasked long-term sequestration of host T cell subsets in human skin despite complete donor T cell chimerism in the blood. Single-cell chimerism analysis paired with single-cell transcriptional profiling comprehensively characterized these bona fide long-term skin-resident T cells and revealed differential tissue maintenance for distinct T cell subsets, specific T-RM cell markers such as galectin-3, but also tissue exit potential with retention of the transcriptomic T-RM cell identity. Analysis of 26 allo-HSCT patients revealed profound interindividual variation in the tissue maintenance of host skin T cells. The long-term persistence of host skin T cells in a subset of these patients did not correlate with the development of chronic GvHD. Our data exemplify the power of exploiting a clinical situation as a proof of concept for the existence of bona fide human skin T-RM cells and reveal long-term persistence of host T cells in a peripheral tissue but not in the circulation or bone marrow in a subset of allo-HSCT patients.
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