Rethinking T cell mediated graft rejection – what the immune cell landscape tells us about organ rejection

The role of effector T cells in mediating allograft rejection (T cell-mediated rejection (TCMR) was first described in the 1950s, resulting in the future development of a plethora of effective anti-rejection therapies targeting T cells. Therefore, transplant research at large shifted focus to antibody-mediated rejection which currently has few treatment options. However, despite the success of these immunosuppressants to improve short-term graft survival, acute TCMR still has a 10% incident rate while chronic, recurrent TCMR occurs in 40% of all grafts and remains a significant barrier to long-term graft survival. This emphasizes a critical need for the resurgence of research aimed at defining the multifactorial immunological mechanisms of TCMR that underlie the heterogeneity in response to treatment. Recent advances in the histological, genomic, and single-cell analysis of rejected grafts indicate that TCMR is driven by a diverse set of immune cell populations including macrophages, dendritic cells, B cells, and novel T cell subsets. Single-cell RNAseq and multiplex imaging studies highlight the complicated ties between Th1, 2, and 17 cells along with memory CD8+ T cells that mediate rejection. A deeper understanding of how these cell populations interact to influence allorecognition, T cell receptor signaling, and response to therapy will lead to better biomarkers for early TCMR detection, refine treatment options and provide novel protein targets for improved therapeutic interventions.

The purpose of this research topic is to strengthen our understanding of acute and chronic TCMR by highlighting recent studies focused on the interrogation of the immune cell landscape within transplanted organs and the interplay between these populations that promotes the development and persistence of TCMR.

In this Research Topic, the submission of both Original Research and Review articles are welcome, including but not limited to the following subtopics:

1. Multi-omics analysis of TCMR
2. Molecular mechanisms of T cell activation and regulation driving TCMR
3. Novel infiltrating immune cell populations correlating with TCMR response to therapy
4. Novel protein targets for the prevention or treatment of TCMR
5. Advances in the histological identification of acute and chronic TCMR
6. Biomarker discovery for TCMR
7. Novel treatments for TCMR including small molecules or CAR-T therapies
8. Treatment-resistant TCMR in kidney transplantation: real-world evidence
9. Current treatments for TCMR in kidney transplantation: intended mechanisms and adverse effects