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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Base Sequence
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Cytomegalovirus / immunology*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunologic Memory / immunology*
  • Interleukin-7 Receptor alpha Subunit / metabolism
  • Leukocyte Common Antigens / metabolism
  • Lymphocyte Count
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, CCR7 / metabolism
  • Sequence Analysis, DNA
  • Stem Cells / immunology*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • fas Receptor / metabolism


  • CCR7 protein, human
  • CD8 Antigens
  • FAS protein, human
  • Interleukin-7 Receptor alpha Subunit
  • Receptors, Antigen, T-Cell
  • Receptors, CCR7
  • fas Receptor
  • Leukocyte Common Antigens