Human DPTs directly involved in GVHD pathogenesis

Hess NJ, Turicek DP, Capitini CM, et al. Inflammatory CD4/CD8 Double-Positive Human T Cells Arise from Reactive CD8 T Cells and Are Sufficient to Mediate GVHD Pathology. Science Advances. 2023; 9 (12) (doi: 10.1126/sciadv.adf0567).

Researchers report that a unique population of double-positive CD4/CD8 human T-cells (DPT) is directly implicated in the pathogenesis of graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (allo-HCT). In their small, single-site study involving 35 patients, investigators determined that the highly inflammatory cells — which they found to be transcriptionally, metabolically, and phenotypically different from their single-positive counterparts — are not present in healthy human grafts. Rather, they surface post-allo-HCT in response to antigenic stimulation; and their presence appears to be a robust predictor of grade 2 or higher GVHD. In a xenogeneic transplant model, isolated DPTs retransplanted into naive mice mediated xeno-GVHD pathology. However, no survival benefit was documented in mice challenged with human B-ALL malignancies, indicating DPT CD4/CD8 T cells influence GVHD development but not graft-versus-leukemia function.

Read More

Tags: astct, GVHD, Transplant, Acute GVHD, cell therapy, T-Cell, survival rate, T cell