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The role of \u03b3\u03b4 T\u00a0cells in the context of CAR\u2010T cell therapy remains poorly understood. This study investigates the transcriptional heterogeneity, clonal expansion and dynamics of \u03b3\u03b4 T\u00a0cells in patients undergoing anti\u2010CD19 CAR\u2010T cell therapy. Longitudinal single cell multi\u2010omics analysis was performed on \u03b3\u03b4 T\u00a0cells from four patients receiving anti\u2010CD19 CAR\u2010T cell therapy. Single cell RNA\u2010seq, antibody\u2010based protein profiling (AbSeq) and full\u2010length TCR\u03b3\u03b4 sequences revealed clonally expanded populations displaying plasticity in T\u00a0cell differentiation, and temporal dynamics of large clones, suggesting ongoing expansion and differentiation. Clonally expanded \u03b3\u03b4 T\u00a0cells had heterogeneous gene expression profiles, occupying seven transcriptionally distinct clusters. Analysis of chemokine markers indicated cluster\u2010specific homing tendencies of circulating \u03b3\u03b4 T\u00a0cells to peripheral tissues. We found unexpectedly high frequencies of V\u03b41 and V\u03b43 cells in the blood with distinct gene and protein expression profiles. This analysis provides insights into the dynamic and heterogeneous nature of \u03b3\u03b4 T\u00a0cells following anti\u2010CD19 CAR\u2010T cell therapy, contributing valuable information for optimizing CAR\u2010T cell therapies in B cell malignancies.<\/jats:p>","DOI":"10.1111\/imcb.12834","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:25:33Z","timestamp":1730852733000},"page":"60-72","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of clonally expanded \u03b3\u03b4 T\u2010cell populations during CAR\u2010T\u00a0cell therapy"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8803-0700","authenticated-orcid":false,"given":"Arman","family":"Safavi","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences UNSW Sydney  Sydney NSW 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