Immune cells play important roles in mediating allograft rejection and tolerance after cardiac transplantation. However, immune cell heterogeneity at the single-cell level, and how immune cell states shape transplantation immunity, remain incompletely characterized.

The authors of a new study, published in Cardiovascular Innovations and Applications, performed single-cell RNA sequencing (scRNA-seq) on immune cells in LNs from a mouse syngeneic and allogeneic cardiac transplantation model. Nine T cell clusters were identified through unsupervised analysis. Pathway enrichment analysis was used to explore the functional differences among cell subpopulations and to characterize the metabolic heterogeneity of T cells.

The transcriptional landscape of immune cells was determined, particularly T cells, and their metabolic transcriptomes in LNs during mouse cardiac transplantation. On the basis of molecular and functional properties, we also identified T cell types associated with transplantation-associated immune processes, including cytotoxic CD8⁺ T cells, activated conventional CD4⁺ T cells, and dysfunctional Tregs. The contribution of JunB to the induction of Th17 cell differentiation and restriction of Treg development was further elucidated, and the authors identified that HIF-1a participates in T cell metabolism and function.

The first systematic single-cell analysis of transcriptional variation within the T cell population is presented in this article, providing new insights for the development of novel therapeutic targets for allograft rejection.

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