Dual receptor T cells mediate pathologic alloreactivity in patients with acute graft-versus-host disease

Gerald P. Morris, Geoffrey L. Uy, David Donermeyer, John F. DiPersio, Paul M. Allen

Research output: Contribution to journalArticle

24 Scopus citations

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.

Original languageEnglish
Article number188ra74
JournalScience translational medicine
Volume5
Issue number188
DOIs
StatePublished - Jun 5 2013

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