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 journalArticle

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

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Hematopoietic Stem Cell Transplantation
T-Lymphocytes
Antigens
Human Herpesvirus 4
HLA-A24 Antigen
MART-1 Antigen
Gene Expression
Cell Line
Jurkat Cells
Histocompatibility Antigens Class II
Virus Diseases
T-Cell Antigen Receptor
Autoimmunity
Interleukin-8
varespladib methyl
Population
Communicable Diseases

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)

Cite this

Ahmed, R. K., Poiret, T., Ambati, A., Rane, L., Remberger, M., Omazic, B., ... Maeurer, M. (2014). TCR+CD4-CD8- T cells in antigen-specific MHC class I-restricted T-cell responses after allogeneic hematopoietic stem cell transplantation. Journal of Immunotherapy, 37(8), 416-425.

TCR+CD4-CD8- T cells in antigen-specific MHC class I-restricted T-cell responses after allogeneic hematopoietic stem cell transplantation. / Ahmed, Raija K.; Poiret, Thomas; Ambati, Aditya; Rane, Lalit; Remberger, Mats; Omazic, Birgitta; Vudattu, Nalini K.; Winiarski, Jacek; Ernberg, Ingemar; Axelsson-Robertson, Rebecca; Magalhaes, Isabelle; Castelli, Chiara; Ringden, Olle; Maeurer, Markus.

In: Journal of Immunotherapy, Vol. 37, No. 8, 01.10.2014, p. 416-425.

Research output: Contribution to journalArticle

Ahmed, RK, Poiret, T, Ambati, A, Rane, L, Remberger, M, Omazic, B, Vudattu, NK, Winiarski, J, Ernberg, I, Axelsson-Robertson, R, Magalhaes, I, Castelli, C, Ringden, O & Maeurer, M 2014, 'TCR+CD4-CD8- T cells in antigen-specific MHC class I-restricted T-cell responses after allogeneic hematopoietic stem cell transplantation', Journal of Immunotherapy, vol. 37, no. 8, pp. 416-425.
Ahmed, Raija K. ; Poiret, Thomas ; Ambati, Aditya ; Rane, Lalit ; Remberger, Mats ; Omazic, Birgitta ; Vudattu, Nalini K. ; Winiarski, Jacek ; Ernberg, Ingemar ; Axelsson-Robertson, Rebecca ; Magalhaes, Isabelle ; Castelli, Chiara ; Ringden, Olle ; Maeurer, Markus. / TCR+CD4-CD8- T cells in antigen-specific MHC class I-restricted T-cell responses after allogeneic hematopoietic stem cell transplantation. In: Journal of Immunotherapy. 2014 ; Vol. 37, No. 8. pp. 416-425.
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