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- Title
Healthy-like CD4 + Regulatory and CD4 + Conventional T-Cell Receptor Repertoires Predict Protection from GVHD Following Donor Lymphocyte Infusion.
- Authors
Schneider, Jessica; Kuhlmann, Leonie; Xiao, Yankai; Raha, Solaiman; Bernhardt, Günter; Stadler, Michael; Thol, Felicitas; Heuser, Michael; Eder, Matthias; Ganser, Arnold; Ravens, Sarina; Förster, Reinhold; Prinz, Immo; Koenecke, Christian; Schultze-Florey, Christian R.
- Abstract
Donor lymphocyte infusion (DLI) can (re-)induce durable remission in relapsing patients after allogeneic hematopoietic stem-cell transplantation (alloHSCT). However, DLI harbors the risk of increased non-relapse mortality due to the co-occurrence of graft-versus-host disease (GVHD). GVHD onset may be caused or accompanied by changes in the clonal T-cell receptor (TCR) repertoire. To investigate this, we analyzed T cells in a cohort of 21 patients receiving DLI after alloHSCT. We performed deep T-cell receptor β (TRB) sequencing of sorted CD4+CD25+CD127low regulatory T cells (Treg cells) and CD4+ conventional T cells (Tcon cells) in order to track longitudinal changes in the TCR repertoire. GVHD following DLI was associated with less diverse but clonally expanded CD4+CD25+CD127low Treg and CD4+ Tcon TCR repertoires, while patients without GVHD exhibited healthy-like repertoire properties. Moreover, the diversification of the repertoires upon GVHD treatment was linked to steroid-sensitive GVHD, whereas decreased diversity was observed in steroid-refractory GVHD. Finally, the unbiased sample analysis revealed that the healthy-like attributes of the CD4+CD25+CD127low Treg TCR repertoire were associated with reduced GVHD incidence. In conclusion, CD4+CD25+CD127low Treg and CD4+ Tcon TRB repertoire dynamics may provide a helpful real-time tool to improve the diagnosis and monitoring of treatment in GVHD following DLI.
- Subjects
REGULATORY T cells; LYMPHOCYTES; T cell receptors; CD4 antigen; STEM cell transplantation; GRAFT versus host disease
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 18, pN.PAG
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms231810914