TCR+CD4-CD8- T cells in antigen-specific MHC class I-restricted T-cell responses after allogeneic hematopoietic stem cell transplantation

Raija K. Ahmed, Thomas Poiret, Aditya Ambati, Lalit Rane, Mats Remberger, Birgitta Omazic, Nalini K. Vudattu, Jacek Winiarski, Ingemar Ernberg, Rebecca Axelsson-Robertson, Isabelle Magalhaes, Chiara Castelli, Olle Ringden, Markus Maeurer

Research output: Contribution to journalArticlepeer-review

Abstract

Human TCRαβ+ CD4-CD8- double-negative (DN) T cells represent a minor subset in peripheral blood, yet are important in infectious diseases and autoimmune responses. We examined the frequency of DN T cells in 17 patients after allogeneic hematopoietic stem cell transplantation (aHSCT) at 1, 2, 3, 6, and 12 months post-aHSCT and show that these cells increase early after aHSCT and decrease with time after aHSCT. DN T cells reside in the terminally differentiated effector (CD45RA+ CCR7-) T-cell population and are polyclonal, determined by T-cell receptor Vb CDR3 analysis. Gene expression analysis of ex vivo sorted DN T cells showed a distinct set of gene expression, including interleukin-8, as compared with CD4+ or CD8+ T cells. DN T cells contributed to MHC class I-restricted EBV-directed immune responses, defined by antigen-specific cytokine production and by detection of HLA-A02: 01-restricted EBV BMLF-1 (GLCTLVAML), LMP-2A (CLGGLLTMV), and HLA-A24: 02-restricted EBV BRLF-1 (DYCNVLNKEF) and EBNA3 (RYSIFFDY)-specific T cells. We created retroviral-transfected Jurkat cell lines with a Melan-A/MART-1-specific TCR+ and the CD8α chain to study TCR+ DN T cells in response to their nominal MHC class I/peptide ligand. We show that DN T cells exhibit increased TCRζ chain phosphorylation as compared with the TCR+ CD8+ transgenic T-cell line. DN T cells contribute to antigen-specific T-cell responses and represent an effector T-cell population that may be explored in immunother-apeutic approaches against viral infections or transformed cells.

Original languageEnglish
Pages (from-to)416-425
Number of pages10
JournalJournal of Immunotherapy
Volume37
Issue number8
Publication statusPublished - Oct 1 2014

Keywords

  • aHSCT
  • DN T cells
  • EBV
  • Immune reconstitution
  • Retroviral TCR transfer
  • T cells
  • Tetramer

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Cancer Research
  • Pharmacology
  • Medicine(all)

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