CMV Shapes Immune Recovery Post-Transplant
NK and T cell repertoire is established early after allogeneic HSCT and is profoundly imprinted by CMV reactivation
Besides genetic influences, non-genetic factors such as graft-versus-host disease (GvHD) and viral infections have been shown as important shapers of the immune reconstitution and diversification processes after hematopoietic stem cell transplantation (HSCT). However, the differential susceptibility to immune modulation by non-genetic factors is not fully understood. The authors of this article, led by GCIR Professor Jean Villard, determined to follow the reconstitution of the T cell receptor (TCR) repertoire through immune-sequencing, of natural killer (NK) cells using a 35-marker spectral flow cytometry panel, and in relation to clinical events. Longitudinal investigation was performed on samples derived from 54 HSCT recipients during the first-year post-HSCT. They confirmed a significant contraction in TCR repertoire diversity with a remarkable stability over time. CMV reactivation had the ability to significantly change TCR repertoire clonality and composition, with a long-lasting imprint. Their data further revealed skewing of NK cell reconstitution in CMV reactivated recipients, with an increased frequency of KIR2DL2L3S2+ adaptive, cytolytic and functional CD107a+ NK cells concomitant with a reduced pool of NKG2A+ NK cells. They provided support that CMV might act as one of the more important driver of peripheral homeostatic proliferation of circulating specific T and NK cells, which can be viewed as a compensatory mechanism to establish a new peripheral repertoire.
Full article: https://doi.org/10.1182/bloodadvances.2024013117
Funding: This study was supported by the Academic Society of the University of Geneva, IRGHET (International Research Group on unrelated Hematopoietic stem cell Transplantation), the Dr Henri Dubois-Ferrière Dinu Lippatti Foundation, the Philanthropy Settlement, the Fondation de Reuter and the NIH.
Why is it important?
After a bone marrow transplant, the immune system rebuilds, but factors like infections can influence this process. This study followed 54 patients for a year and found that Cytomegalovirus (CMV) reactivation has a big impact on the types of T cells and NK cells in the body. CMV causes these immune cells to expand and change in ways that help fight infections and potentially prevent cancer relapse. The study showed that these immune changes are stable for at least a year, suggesting that CMV is a key player in immune system recovery after transplants. Understanding this could lead to better ways to manage and protect patients post-transplantation.