Allogeneic Stem Cell Transplants Improve Microbiome, Immune Cells

Past studies have suggested ties between microbial diversity and favorable allogeneic hematopoietic stem cell transplantation (allo-HCT) outcomes, or transplants involving stem cells from healthy donors. The interactions between the gut microbial community and the immune system can influence an individual's response to a bone marrow transplant to treat leukemia, lymphoma, multiple myeloma, and other blood conditions.

It has been reported that a diverse intestinal microbiome at early times after allo-HCT is associated with higher numbers of innate-like mucosal-associated invariant T (MAIT) cells, and this correlated with a higher prevalence of the Vδ2 subpopulation of γδ T cells and a reduced incidence of acute graft-versus-host disease (aGVHD).

A large team of clinical scientists led by the Weill Cornell Medical College (New York, NY, USA) used targeted 16S ribosomal RNA sequencing on fecal samples, as well as flow cytometry-based immune cell profiling in peripheral blood samples, and searched for outcome-related features in 174 allo-HCT recipients. The analyses pointed to an uptick in mucosal-associated invariant T (MAIT) immune cells in individuals with lower rates of acute graft-versus-host disease complications, better stem cell transplant outcomes, and increased survival times.

Immune profiling of conventional and unconventional immune cell subsets revealed that the prevalence of Vδ2 cells, the major circulating subpopulation of γδ T cells, closely correlated with the frequency of MAIT cells and was associated with less aGVHD. Analysis of these populations using both single-cell transcriptomics and flow cytometry suggested a shift toward activated phenotypes and a gain of cytotoxic and effector functions after transplantation.

Among other gut microbial ties, the team found that higher-than-usual MAIT levels in blood samples from the allo-HCT recipients tended to correspond with the presence of gut bacteria from the Bacteroidetes phylum, while decreased blood levels of the T cells turned up in those with Firmicutes-rich gut microbiomes. A diverse intestinal microbiome with the capacity to produce activating ligands for MAIT and Vδ2 cells appeared to be necessary for the maintenance of these populations after allo-HCT. These data suggest an immunological link between intestinal microbial diversity, microbe-derived ligands, and maintenance of unconventional T cells.

Kate Markey, MBBS, PhD, FRACP, an Immunologist and co-senior author of the study, said, “There is a growing awareness in the transplant field that a healthy, diverse microbiome is linked with good outcome. Ways to prevent damage and restore a healthy microbiome are both going to be important and are the subject of active clinical trials now. The study was published on May 25, 2022 in the journal Science Translational Medicine.

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