title: Adenovirus-specific T-cell Subsets in Human Peripheral Blood and After IFN-γ Immunomagnetic Selection.
abstract: Adoptive antiviral cellular immunotherapy by infusion of virus-specific T cells (VSTs) is becoming an alternative treatment for viral infection after hematopoietic stem cell transplantation. The T memory stem cell (TSCM) subset was recently described as exhibiting self-renewal and multipotency properties which are required for sustained efficacy in vivo. We wondered if such a crucial subset for immunotherapy was present in VSTs. We identified, by flow cytometry, TSCM in adenovirus (ADV)-specific interferon (IFN)-γ+ T cells before and after IFN-γ-based immunomagnetic selection, and analyzed the distribution of the main T-cell subsets in VSTs: naive T cells (TN), TSCM, T central memory cells (TCM), T effector memory cell (TEM), and effector T cells (TEFF). In this study all of the different T-cell subsets were observed in the blood sample from healthy donor ADV-VSTs, both before and after IFN-γ-based immunomagnetic selection. As the IFN-γ-based immunomagnetic selection system sorts mainly the most differentiated T-cell subsets, we observed that TEM was always the major T-cell subset of ADV-specific T cells after immunomagnetic isolation and especially after expansion in vitro. Comparing T-cell subpopulation profiles before and after in vitro expansion, we observed that in vitro cell culture with interleukin-2 resulted in a significant expansion of TN-like, TCM, TEM, and TEFF subsets in CD4IFN-γ T cells and of TCM and TEM subsets only in CD8IFN-γ T cells. We demonstrated the presence of all T-cell subsets in IFN-γ VSTs including the TSCM subpopulation, although this was weakly selected by the IFN-γ-based immunomagnetic selection system.
authors.affiliation: *Nancy University Hospital, Cell and Tissue Banking Unit and Research Federation FR 3209 ‡Nancy University Hospital, Immunology Laboratory and Nancytomique Platform §Nancy University Hospital, Allogeneic Hematopoietic Stem Cell Transplant Unit †Lorraine University, UMR CNRS 7365 and FR 3209 CNRS-INSERM-UL-CHU, Vandoeuvre-Lés-Nancy ∥Lorraine University, Microbiology-Immunology department, Faculty of Pharmacy, Nancy, France.
authors.forename: Chongsheng
authors.initials: C
authors.lastname: Qian
authors.forename: Yingying
authors.initials: Y
authors.lastname: Wang
authors.forename: Huili
authors.initials: H
authors.lastname: Cai
authors.forename: Caroline
authors.initials: C
authors.lastname: Laroye
authors.forename: Marcelo
authors.initials: M
authors.lastname: De Carvalho Bittencourt
authors.forename: Laurence
authors.initials: L
authors.lastname: Clement
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Stoltz
authors.forename: Véronique
authors.initials: V
authors.lastname: Decot
authors.forename: Loïc
authors.initials: L
authors.lastname: Reppel
authors.forename: Danièle
authors.initials: D
authors.lastname: Bensoussan
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000257:Adenoviridae Infections / Q000276:immunology / Q000628:therapy; D000954:Antigens, Surface / Q000378:metabolism; D018929:Cell Culture Techniques; D003602:Cytotoxicity, Immunologic; D064368:Healthy Volunteers; D006801:Humans; D007156:Immunologic Memory; D018189:Immunomagnetic Separation; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000378:metabolism*; D018655:Lymphocyte Count; D010641:Phenotype; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000954:Antigens, Surface; D007371:Interferon-gamma