Lakshmikanth, T;
Heuts, F;
Muvva, SJ;
Wallin, RP;
Persson, AK;
Fauriat, C;
Applequist, SE;
... Juarez, JG; + view all
(2016)
In vivo engineering of mobilized stem cell grafts with the immunomodulatory drug FTY720 for allogeneic transplantation.
European Journal of Immunology
, 46
(7)
pp. 1758-1769.
10.1002/eji.201545991.
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Lakshmikanth_et_al-2016 In vivo engineering of mobilized stem cell grafts with the immunomodulatory drug FTY720 for allogeneic transplantation VOR.pdf Download (3MB) | Preview |
Abstract
The immunological attributes of stem cell grafts play an important role in the outcome of allogeneic stem cell transplants. Currently, ex vivo manipulation techniques such as bulk T cell depletion or positive selection of CD34(+) cells are utilized to improve the immunological attributes of grafts and minimize the potential for graft-versus-host disease (GvHD). Here, we demonstrate a novel graft engineering technique, which utilizes the immunomodulatory drug FTY720 for in vivo depletion of naïve T (TN ) cells from donor G-CSF-mobilized grafts without ex vivo manipulation. We show that treatment of donor mice with FTY720 during mobilization depletes grafts of TN cells and prevents lethal GvHD following transplantation in a major mismatch setting. Importantly, both stem cells and NK cells are retained in the FTY720-treated grafts. FTY720 treatment does not negatively affect the engraftment potential of stem cells as demonstrated in our congenic transplants or the functionality of NK cells. In addition, potentially useful memory T cells may be retained in the graft. These findings suggest that FTY720 may be used to optimize the immunological attributes of G-CSF-mobilized grafts by removing potentially deleterious TN cells which can contribute to GvHD, and by retaining useful cells which can promote immunity in the recipient.
| Type: | Article |
|---|---|
| Title: | In vivo engineering of mobilized stem cell grafts with the immunomodulatory drug FTY720 for allogeneic transplantation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/eji.201545991 |
| Publisher version: | http://dx.doi.org/10.1002/eji.201545991 |
| Language: | English |
| Additional information: | Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
| Keywords: | Allogeneic stem cell transplantation, Graft engineering, Graft-versus-host disease, Stem cell mobilization, T cells |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1489840 |
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