title: Regulatory T cells inhibit CD34+ cell differentiation into NK cells by blocking their proliferation.
abstract: 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.
authors.affiliation: Anthony Nolan Research Institute and University College London, Royal Free Campus, Pond Street, London NW3 2QG, UK.
authors.forename: Isabela
authors.initials: I
authors.lastname: Pedroza-Pacheco
authors.affiliation: Anthony Nolan Research Institute and University College London, Royal Free Campus, Pond Street, London NW3 2QG, UK.
authors.forename: Divya
authors.initials: D
authors.lastname: Shah
authors.affiliation: Anthony Nolan Research Institute and University College London, Royal Free Campus, Pond Street, London NW3 2QG, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Domogala
authors.affiliation: Anthony Nolan Research Institute and University College London, Royal Free Campus, Pond Street, London NW3 2QG, UK.
authors.forename: Martha
authors.initials: M
authors.lastname: Luevano
authors.affiliation: Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Blundell
authors.affiliation: Anthony Nolan Research Institute and University College London, Royal Free Campus, Pond Street, London NW3 2QG, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Jackson
authors.affiliation: Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Adrian
authors.initials: A
authors.lastname: Thrasher
authors.affiliation: Anthony Nolan Research Institute and University College London, Royal Free Campus, Pond Street, London NW3 2QG, UK.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Madrigal
authors.affiliation: Anthony Nolan Research Institute and University College London, Royal Free Campus, Pond Street, London NW3 2QG, UK.
authors.forename: Aurore
authors.initials: A
authors.lastname: Saudemont
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D049109:Cell Proliferation; D006410:Hematopoiesis; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000502:physiology*; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000502:physiology*