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Cord blood-derived T cells allow the generation of a more naïve tumor-reactive cytotoxic T-cell phenotype

Authors :
Martin Sauer
Britta Eiz-Vesper
Julian Kwoczek
Mathias Oelke
Rainer Blasczyk
Szilvia Bak
Holger Maul
Sabine Tischer
Julia Lahrberg
Sebastian B. Riese
Source :
Transfusion. 58:88-99
Publication Year :
2017
Publisher :
Wiley, 2017.

Abstract

BACKGROUND Transplantation of hematopoietic stem cells (HSCs) from peripheral blood (PB) or cord blood (CB) is well established. HSCs from CB are associated with a lower risk of graft-versus-host disease (GVHD), but antigen-independent expanded CB- and PB-derived T cells can induce GVHD in allo-HSC recipients. CB-derived cells might be more suitable for adoptive immunotherapy as they have unique T-cell characteristics. Here, we describe functional differences between CB and PB T cells stimulated with different cytokine combinations involved in central T-cell activation. STUDY DESIGN AND METHODS Isolated CD8+ T cells from CB and PB were stimulated antigen independently with anti-CD3/CD28 stimulator beads or in an antigen-dependent manner with artificial antigen-presenting cells loaded with the HLA-A*02:01-restricted peptide of tumor-associated melanoma antigen recognized by T cells 1 (MART1). CB and PB T cells cultured in the presence of interleukin (IL)-7, IL-15, IL-12, and IL-21 were characterized for T-cell phenotype and specificity, that is, by CD107a, interferon-γ, tumor necrosis factor-α, and IL-2 expression. RESULTS After antigen-independent stimulation, activated CD8+ CB T cells exhibited stronger proliferation and function than those from PB. After antigenic stimulation, MART1-reactive CB T cells were naive (CD45RA+CCR7+), cytotoxic, and highly variable in expressing homing marker CD62L. Addition of IL-21 resulted in increased T-cell proliferation, whereas supplementation with IL-12 decreased IL-21–induced expansion, but increased the functionality and cytotoxicity of CB and PB T cells. CONCLUSION MART1-reactive CB T cells with a more naive phenotype and improved properties for homing can be generated. The results contribute to better understanding the effects on GVHD and graft versus tumor.

Details

ISSN :
00411132
Volume :
58
Database :
OpenAIRE
Journal :
Transfusion
Accession number :
edsair.doi...........052d1ad2f9f393be6001832c61ff2e72
Full Text :
https://doi.org/10.1111/trf.14365