30 Day Post HSCT Human CD3+ RNA-seq

The precise control of allogeneic T-cell responses is critical for successful allogeneic hematopoietic stem cell transplantation (HSCT). These responses include the desirable graft versus leukemia effect and the undesirable graft versus host disease. However, the mechanisms governing allogeneic T-cell responses remain incompletely understood which limits the wider application of HSCT. We hypothesized that allogeneic T-cell responses are controlled by the recently identified immune-regulatory non-coding RNA genes, called long non-coding-RNAs (lncRNA). To test this, we sought to identify and characterize differentially-expressed lncRNAs in human allogeneic T-cells. RNA-sequencing was used to identify lncRNAs expressed in donor CD3+ T-cells on day 30 post HSCT from matched unrelated donor (MUD) and mis-matched unrelated donor (MMUD) HSCT patients relative to autologous (Auto) HSCT patients. Relative to autologous controls, lncRNA differential expression was only observed in the MMUD group. The bulk of differentially expressed lncRNAs showed increasing expression with increasing allo-stimulation (i.e. higher expression in the MMUD group), as would be expected upon T-cell activation. These results indicate that lncRNA differential expression in allogeneic T-cells correlates with the strength of the allogeneic stimulus they receive.