Researchers from the Dana-Farber Cancer Institute Boston, MA have uncovered an important mechanism for organ infiltration by pathogenic donor CD8+ TRM cells during acute graft-versus-host disease (aGVHD). Hematopoietic cell transplantation (HCT) can be used to treat certain types of cancers, but this can lead to aGVHD, where the donated blood cells infiltrate and attack the recipient’s organs.
Evidence suggests that donor T cells, which mediate immune attack, acquire tissue-resident memory (TRM) and remain in specific organs during aGVHD. This study sought to understand the mechanism by which T cells infiltrate donor tissue using a non-human primate model of aGVHD. By using serial intravascular staining (SIVS) followed by multiparameter flow cytometric, and single-cell transcriptomics, the authors were able to dissect how and when donor T cells occupy tissues.
The authors found that the cytotoxic TRM phenotype was rapidly acquired (within 8 days after transplant), as donor CD8+ T cells infiltrate tissues. Furthermore, these cells expressed specific active/invasive gene signatures driven by interleukin-15 (IL-15)/IL-21 signaling including cell-adhesion proteins (ITGB2), specific chemokines (CCL3 and CCL4L1) and chemokine receptors (CD74). Taken together, this study provides important insight into the transcriptional networks activated during TRM cell infiltration, which may allow development of new therapies for GVHD.
Tkachev V, Kaminski J, Potter EL, et al. Spatiotemporal single-cell profiling reveals that invasive and tissue-resident memory donor CD8+ T cells drive gastrointestinal acute graft-versus-host disease. Sci Transl Med. 13(576):eabc0227 (2021).