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J Immunol. 2015 Jun 1;194(11):5559-67. doi: 10.4049/jimmunol.1402090. Epub 2015 Apr 27.

Peripheral blood-derived virus-specific memory stem T cells mature to functional effector memory subsets with self-renewal potency.

Author information

1
Institute for Medical Immunology, Charité University Medicine Berlin, D-13353 Berlin, Germany; Renal and Transplant Research Unit, Department of Nephrology and Internal Intensive Care, Charité University Medicine Berlin, D-13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine Berlin, D-13353 Berlin, Germany; michael.schmueck-henneresse@charite.de.
2
Institute for Medical Immunology, Charité University Medicine Berlin, D-13353 Berlin, Germany;
3
Renal and Transplant Research Unit, Department of Nephrology and Internal Intensive Care, Charité University Medicine Berlin, D-13353 Berlin, Germany;
4
Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine Berlin, D-13353 Berlin, Germany; Berlin-Brandenburg School for Regenerative Therapies, Charité University Medicine Berlin, D-13353 Berlin, Germany; Department for Pediatric Pulmonology and Immunology, Charité University Medicine Berlin, D-13353 Berlin, Germany;
5
Renal and Transplant Research Unit, Department of Nephrology and Internal Intensive Care, Charité University Medicine Berlin, D-13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine Berlin, D-13353 Berlin, Germany;
6
Institute for Medical Immunology, Charité University Medicine Berlin, D-13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine Berlin, D-13353 Berlin, Germany;
7
Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine Berlin, D-13353 Berlin, Germany; Marien Hospital Herne, Ruhr University Bochum, D-44625 Herne, Germany; and.
8
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030.

Abstract

Memory T cells expressing stem cell-like properties have been described recently. The capacity of self-renewal and differentiation into various memory/effector subsets make them attractive for adoptive T cell therapy to combat severe virus infections and tumors. The very few reports on human memory stem T cells (T(SCM)) are restricted to analyses on polyclonal T cells, but extensive data on Ag-specific T(SCM )are missing. This might be due to their very low frequency limiting their enrichment and characterization. In this article, we provide functional and phenotypic data on human viral-specific T(SCM), defined as CD8(+)CD45RA(+)CCR7(+)CD127(+)CD95(+). Whereas <1% of total T cells express the T(SCM) phenotype, human CMV-specific T(SCM) can be detected at frequencies similar to those seen in other subsets, resulting in ∼ 1 /10,000 human CMV-specific T(SCM). A new virus-specific expansion protocol of sort-purified T(SCM) reveals both upregulation of various T cell subset markers and preservation of their stem cell phenotype in a significant proportion, indicating both self-renewal and differentiation potency of virus-specific T cells sharing their TCR repertoire. Furthermore, we describe a simplified culture protocol that allows fast expansion of virus-specific T(SCM) starting from a mixed naive T/T(SCM) pool of PBLs. Due to the clinical-grade compatibility, this might be the basis for novel cell therapeutic options in life-threatening courses of viral and tumor disease.

PMID:
25917088
DOI:
10.4049/jimmunol.1402090
[Indexed for MEDLINE]
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