Inflammatory CD4/CD8 double-positive human T cells arise from reactive CD8 T cells and are sufficient to mediate GVHD pathology. Sci Adv 2023 Mar 24;9(12):eadf0567
Date
03/25/2023Pubmed ID
36961891Pubmed Central ID
PMC10038349DOI
10.1126/sciadv.adf0567Scopus ID
2-s2.0-85151044773 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
An important paradigm in allogeneic hematopoietic cell transplantations (allo-HCTs) is the prevention of graft-versus-host disease (GVHD) while preserving the graft-versus-leukemia (GVL) activity of donor T cells. From an observational clinical study of adult allo-HCT recipients, we identified a CD4+/CD8+ double-positive T cell (DPT) population, not present in starting grafts, whose presence was predictive of ≥ grade 2 GVHD. Using an established xenogeneic transplant model, we reveal that the DPT population develops from antigen-stimulated CD8 T cells, which become transcriptionally, metabolically, and phenotypically distinct from single-positive CD4 and CD8 T cells. Isolated DPTs were sufficient to mediate xeno-GVHD pathology when retransplanted into naïve mice but provided no survival benefit when mice were challenged with a human B-ALL cell line. Overall, this study reveals human DPTs as a T cell population directly involved with GVHD pathology.
Author List
Hess NJ, Turicek DP, Riendeau J, McIlwain SJ, Contreras Guzman E, Nadiminti K, Hudson A, Callander NS, Skala MC, Gumperz JE, Hematti P, Capitini CMAuthors
Peiman Hematti MD Professor in the Medicine department at Medical College of WisconsinAmy W. Hudson PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Mice
