The allogeneic HLA-DP-restricted T-cell repertoire provoked by allogeneic dendritic cells contains T cells that show restricted recognition of hematopoietic cells including primary malignant cells
| Autor: | Peter van Balen, Aicha Laghmouchi, Conny Hoogstraten, J.H. Frederik Falkenburg, Inge Jedema |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
HLA-DP Antigens Cell type T-Lymphocytes Graft vs Host Disease Graft vs Leukemia Effect Stimulation HLA-DP Biology Article 03 medical and health sciences 0302 clinical medicine Cell Therapy & Immunotherapy Humans Transplantation Homologous Repertoire Hematopoietic Stem Cell Transplantation Myeloid leukemia Dendritic Cells Hematology Transplantation Haematopoiesis Hematologic Neoplasms Cancer research Female Stem cell 030215 immunology |
| Zdroj: | Haematologica, 104(1), 197-206 Haematologica |
| ISSN: | 1592-8721 0390-6078 |
| DOI: | 10.3324/haematol.2018.193680 |
| Popis: | Stem cell grafts from 10/10 HLA-matched unrelated donors are often mismatched for HLA-DP. In some patients, donor T-cell responses targeting the mismatched HLA-DP allele(s) have been found to induce a specific graft-versus-leukemia effect without coinciding graft-versus-host disease, whereas in other cases significant graft-versus-host disease occurred. Cell-lineage-specific recognition patterns within the allogeneic HLA-DP-specific donor T-cell repertoire could explain the differential clinical effects mediated by donor T cells after HLA-DP-mismatched allogeneic stem cell transplantation. To unravel the composition of the HLA-DP T-cell repertoire, donor T-cell responses were provoked by in vitro stimulation with allogeneic HLA-DP-mismatched monocyte-derived dendritic cells. A strategy including depletion of reactivity against autologous dendritic cells allowed efficient identification and enrichment of allo-reactive T cells upon stimulation with HLA-DP-mismatched dendritic cells. In this study we elucidated that the allogeneic HLA-DP-restricted T-cell repertoire contained T cells with differential cell-lineage-specific recognition profiles. As expected, some of the allogeneic HLA-DP-restricted T cells showed broad recognition of a variety of hematopoietic and non-hematopoietic cell types expressing the targeted mismatched HLA-DP allele. However, a significant proportion of the allogeneic HLA-DP-restricted T cells showed restricted recognition of hematopoietic cells, including primary malignant cells, or even restricted recognition of only myeloid cells, including dendritic cells and primary acute myeloid leukemia samples, but not of other hematopoietic and non-hematopoietic cell types. These data demonstrate that the allogeneic HLA-DP-specific T-cell repertoire contains T cells that show restricted recognition of hematopoietic cells, which may contribute to the specific graft-versus-leukemia effect without coinciding graft-versus-host disease. |
| Databáze: | OpenAIRE |
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