Peripheral Blood–Derived Virus-Specific Memory Stem T Cells Mature to Functional Effector Memory Subsets with Self-Renewal Potency

  • Schmueck-Henneresse M
  • Sharaf R
  • Vogt K
  • et al.
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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 (TSCM) are restricted to analyses on polyclonal T cells, but extensive data on Ag-specific TSCM 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 TSCM, defined as CD8+CD45RA+CCR7+CD127+CD95+. Whereas <1% of total T cells express the TSCM phenotype, human CMV–specific TSCM can be detected at frequencies similar to those seen in other subsets, resulting in ∼1/10,000 human CMV–specific TSCM. A new virus-specific expansion protocol of sort-purified TSCM 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 TSCM starting from a mixed naive T/TSCM 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.

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APA

Schmueck-Henneresse, M., Sharaf, R., Vogt, K., Weist, B. J. D., Landwehr-Kenzel, S., Fuehrer, H., … Volk, H.-D. (2015). Peripheral Blood–Derived Virus-Specific Memory Stem T Cells Mature to Functional Effector Memory Subsets with Self-Renewal Potency. The Journal of Immunology, 194(11), 5559–5567. https://doi.org/10.4049/jimmunol.1402090

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