As a followup to yesterday’s post on following troublemaker cells in patients with lupus, we’d like to highlight a recent paper in Blood that takes a similar approach to studying how the immune system comes back after bone marrow/blood stem cell transplant.
Leslie Kean, MD, PhD
The paper’s findings have implications for making this type of transplant safer and preventing graft-versus-host disease. In a bone marrow/blood stem cell transplant, to fight cancer, doctors are essentially clearing out someone’s immune system and then “planting” a new one with the help of a donor. What this paper shows is how much CMV (cytomegalovirus) distorts the new immune system.
CMV is often thought of as harmless — most adults in the United States have been infected with CMV by age 40 and don’t get sick because of it. But in this situation, CMV’s emergence from the shadows forces some of the new T cells to multiply, dominating the immune system so much that it creates gaps in the rest of the T cell repertoire, which can compromise protective immunity. Other seemingly innocuous viruses like BK cause trouble in immunosuppressed patients after kidney transplant.
The senior author, Leslie Kean, moved from Emory to Seattle Children’s Hospital in 2013, and her team began these studies here in 2010 (a host of Emory/Winship hematologists and immunologists are co-authors). This paper is sort of a mirror image of the Nature Immunology paper on lupus because it also uses next-generation sequencing to follow immune cells with DNA rearrangements — in this case, T cells.
The authors presented this research at a bone marrow transplant conference in February:
Our results reveal new evidence for significant holes in the underlying TCR repertoire in patients who reactivate CMV, suggesting that CMV reactivation is associated with a linked expansion of CMV-specific T cells and a contraction of other clones in the context of post-transplant immune reconstitution.
These data provide compelling evidence that key aspects of immunologic skewing during hematopoietic reconstitution are driven by CMV reactivation, and provide the first molecular evidence that in addition to driving expansion of virus-specific cells, CMV reactivation has a detrimental impact on the integrity and heterogeneity of the rest of the T cell repertoire.
About the author
