Dual Receptor T Cells Mediate Pathologic Alloreactivity in Patients with Acute Graft-Versus-Host Disease
Year: 2013
Type: article
Abstract: Acute graft-versus-host disease (aGVHD) results from a robust response of donor T cells transferred during hematopoietic stem cell transplantation (HSCT) to allogeneic peptide-major histocompatibility complex antigens. Previous investigations have not identified T cell subsets that selectively mediate either protective immunity or pathogenic alloreactivity. We demonstrate that the small subset of peripheral T cells that naturally express two T cell receptors (TCRs) on the cell surface contributes disproportionately to aGVHD in patients after allogeneic HSCT. Dual TCR T cells from patients with aGVHD demonstrate an activated phenotype and produce pathogenic cytokines ex vivo. Dual receptor clones from a patient with symptomatic aGVHD responded specifically to mismatched recipient human leukocyte antigens (HLAs), demonstrating pathologic alloreactivity. Human dual TCR T cells are strongly activated and expanded by allogeneic stimulation in vitro, and disproportionately contribute to the repertoire of T cells recognizing both major (HLA) and minor histocompatibility antigens, providing a mechanism for their observed activity in vivo in patients with aGVHD. These results identify dual TCR T cells as a target for focused analysis of a T cell subset mediating GVHD and as a potential prognostic indicator.
Source: Science Translational Medicine
Institution: Washington University in St. Louis
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: T Cell Recognition of Allogeneic Peptide/MHC Ligands, Investigation of the Molecular Basis of T Cell Alloreactivity, Washington University Institute of Clinical and Translational Sciences, RECOGNITION AND SIGNALING IN POSITIVE SELECTION OF CD4+ T CELLS, Washington University Institute of Clinical and Translational Sciences (UL1), Targeting Leukemia Stromal Interactions in AML, Cancer Center Support Grant
OpenAlex ID: W2103668327