Cord blood-derived T cells allow the generation of a more naïve tumor-reactive cytotoxic T-cell phenotype
| Autor: | Julian, Kwoczek, Sebastian B, Riese, Sabine, Tischer, Szilvia, Bak, Julia, Lahrberg, Mathias, Oelke, Holger, Maul, Rainer, Blasczyk, Martin, Sauer, Britta, Eiz-Vesper |
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| Rok vydání: | 2017 |
| Předmět: |
Interleukins
T-Cell Antigen Receptor Specificity Cell Separation Fetal Blood Lymphocyte Activation Immunotherapy Adoptive Microspheres Immunophenotyping MART-1 Antigen Lysosomal-Associated Membrane Protein 1 Organ Specificity T-Lymphocyte Subsets HLA-A2 Antigen Humans Female Cells Cultured T-Lymphocytes Cytotoxic |
| Zdroj: | Transfusion. 58(1) |
| ISSN: | 1537-2995 |
| Popis: | 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.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.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.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. |
| Databáze: | OpenAIRE |
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