TY - JOUR
T1 - TCR+CD4-CD8- T cells in antigen-specific MHC class I-restricted T-cell responses after allogeneic hematopoietic stem cell transplantation
AU - Ahmed, Raija K.
AU - Poiret, Thomas
AU - Ambati, Aditya
AU - Rane, Lalit
AU - Remberger, Mats
AU - Omazic, Birgitta
AU - Vudattu, Nalini K.
AU - Winiarski, Jacek
AU - Ernberg, Ingemar
AU - Axelsson-Robertson, Rebecca
AU - Magalhaes, Isabelle
AU - Castelli, Chiara
AU - Ringden, Olle
AU - Maeurer, Markus
PY - 2014/10/1
Y1 - 2014/10/1
N2 - 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-A∗02: 01-restricted EBV BMLF-1 (GLCTLVAML), LMP-2A (CLGGLLTMV), and HLA-A∗24: 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.
AB - 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-A∗02: 01-restricted EBV BMLF-1 (GLCTLVAML), LMP-2A (CLGGLLTMV), and HLA-A∗24: 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.
KW - aHSCT
KW - DN T cells
KW - EBV
KW - Immune reconstitution
KW - Retroviral TCR transfer
KW - T cells
KW - Tetramer
UR - http://www.scopus.com/inward/record.url?scp=84925817381&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925817381&partnerID=8YFLogxK
M3 - Article
C2 - 25198529
AN - SCOPUS:84925817381
VL - 37
SP - 416
EP - 425
JO - Journal of Immunotherapy
JF - Journal of Immunotherapy
SN - 1053-8550
IS - 8
ER -