Back to Search
Start Over
Cord blood-derived T cells allow the generation of a more naïve tumor-reactive cytotoxic T-cell phenotype.
- Source :
- Transfusion; Jan2018, Vol. 58 Issue 1, p88-99, 12p, 7 Graphs
- Publication Year :
- 2018
-
Abstract
- <bold>Background: </bold>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.<bold>Study Design and Methods: </bold>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.<bold>Results: </bold>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 naïve (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.<bold>Conclusion: </bold>MART1-reactive CB T cells with a more naïve phenotype and improved properties for homing can be generated. The results contribute to better understanding the effects on GVHD and graft versus tumor. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00411132
- Volume :
- 58
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Transfusion
- Publication Type :
- Academic Journal
- Accession number :
- 127166012
- Full Text :
- https://doi.org/10.1111/trf.14365