Regulatory T cells inhibit CD34+ cell differentiation into NK cells by blocking their proliferation
| Autor: | Michael P. Blundell, Martha Luevano, Aurore Saudemont, Divya K. Shah, Adrian J. Thrasher, Alejandro Madrigal, Anna Domogala, Isabela Pedroza-Pacheco, Nicola Jackson |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adoptive cell transfer Cell chemical and pharmacologic phenomena Biology T-Lymphocytes Regulatory Article Cell therapy 03 medical and health sciences Interleukin 21 Mice medicine Animals Humans Cell Proliferation Multidisciplinary Cell growth Hematopoietic stem cell hemic and immune systems medicine.disease Adoptive Transfer Hematopoiesis Killer Cells Natural Haematopoiesis 030104 developmental biology medicine.anatomical_structure Graft-versus-host disease Immunology Cancer research |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep22097 |
| Popis: | Graft versus Host Disease (GvHD) remains one of the main complications after hematopoietic stem cell transplantation (HSCT). Due to their ability to suppress effector cells, regulatory T cells (Tregs) have been proposed as a cellular therapy to prevent GvHD, however they also inhibit the functions of natural killer (NK) cells, key effectors of the Graft versus Leukemia effect. In this study, we have explored whether a Tregs therapy will also impact on NK cell differentiation. Using an in vitro model of hematopoietic stem cell (HSC) differentiation into NK cells, we found that activated Tregs led to a 90% reduction in NK cell numbers when added at the time of commitment to the NK cell lineage. This effect was contact dependent and was reversible upon Tregs depletion. The few NK cells that developed in these cultures were mature and exhibited normal functions. Furthermore, adoptive transfer of activated Tregs in rag-/- γc-/- mice abrogated HSC differentiation into NK cells thus confirming our in vitro findings. Collectively, these results demonstrate for the first time that activated Tregs can inhibit NK cell differentiation from HSC under specific conditions. |
| Databáze: | OpenAIRE |
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