EHA 2021 | Skewed primary antigen-specific responses and chromatin remodelling of T-cells

Arnon Kater, MD, PhD, University of Amsterdam, Amsterdam, The Netherlands, discusses the skewed primary antigen-specific responses and chromatin remodelling of T-cells in a combined OT-I/TCL-1 adoptive transfer model for chronic lymphocytic leukemia (CLL). The study aimed to determine how CLL affects primary antigen-specific T-cell responses. Results from the study showed no significant difference in percentage of total leukemic OT-I cells (CD45.1+CD8+) in wild type and CLL mouse models. However, the T-cell phenotype in wild type mice was skewed by the induction of CLL. Skewing occurred more towards short-lived effector cells and there was an observed lower percentage of effector cells with a memory phenotype. There was also an associated increased expression of effector-related transcription factor T-bet as well as reduced expression of memory-related transcription factor BCL6. Extensive chromatin remodelling within OT-I cells in the CLL mice was also observed. The results from this study suggest a CLL-antigen independent effect on the antigen-specific immune response that drives T-cells towards phenotypes that deem them less functional. This interview took place at the virtual European Hematology Association (EHA) Congress 2021.