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: Chongsheng Qian, Yingying Wang, Huili Cai, Caroline Laroye, Marcelo De Carvalho Bittencourt, Laurence Clement, Jean-François Stoltz, Véronique Decot, Loïc Reppel, Danièle Bensoussan
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) Vol. 39 Issue 1 Pg. 27-35 (Jan 2016) ISSN: 1537-4513 [Electronic] United States
• PMID: 26641259 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Surface
• Interferon-gamma

Topics

• Adenoviridae (immunology)
• Adenoviridae Infections (immunology, therapy)
• Antigens, Surface (metabolism)
• Cell Culture Techniques
• Cytotoxicity, Immunologic
• Healthy Volunteers
• Humans
• Immunologic Memory
• Immunomagnetic Separation
• Immunophenotyping
• Immunotherapy, Adoptive
• Interferon-gamma (metabolism)
• Lymphocyte Count
• Phenotype
• T-Cell Antigen Receptor Specificity (immunology)
• T-Lymphocyte Subsets (immunology, metabolism)