Human skin-resident host T cells can persist long term after allogeneic stem cell transplantation and maintain recirculation potential

Gustavo P. De Almeida, Peter Lichtner, Gertrud Eckstein, Tonio Brinkschmidt, Chang-Feng Chu, Shan Sun, Julian Reinhard, Sophia C. Mädler, Markus Kloeppel, Mareike Verbeek and Christina Zielinski (28 Jan 2022) Science Immunology (Vol 7, Issue 67). DOI: 10.1126/sciimmunol.abe2634 (project B10)

Abstract cited directly from the article:

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.