Carty, Fiona, Corbett, Jennifer, Cunha, João Paulo M. C. M., Reading, James, Tree, Timothy, Ting, Anthony E., Stubblefield, Samatha R. and English, Karen (2018) Multipotent Adult Progenitor Cells Suppress T Cell Activation in In Vivo Models of Homeostatic Proliferation in a Prostaglandin E2-Dependent Manner. Frontiers in Immunology, 6 (645). ISSN 1664-3224
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Abstract
Lymphodepletion strategies are used in the setting of transplantation (including bone
marrow, hematopoietic cell, and solid organ) to create space or to prevent allograft
rejection and graft versus host disease. Following lymphodepletion, there is an excess
of IL-7 available, and T cells that escape depletion respond to this cytokine undergoing
accelerated proliferation. Moreover, this environment promotes the skew of T cells to a
Th1 pro-inflammatory phenotype. Existing immunosuppressive regimens fail to control
this homeostatic proliferative (HP) response, and thus the development of strategies to
successfully control HP while sparing T cell reconstitution (providing a functioning immune
system) represents a significant unmet need in patients requiring lymphodepletion.
Multipotent adult progenitor cells (MAPC®) have the capacity to control T cell proliferation
and Th1 cytokine production. Herein, this study shows that MAPC cells suppressed
anti-thymocyte globulin-induced cytokine production but spared T cell reconstitution in
a pre-clinical model of lymphodepletion. Importantly, MAPC cells administered intraperitoneally
were efficacious in suppressing interferon-γ production and in promoting the
expansion of regulatory T cells in the lymph nodes. MAPC cells administered intraperitoneally
accumulated in the omentum but were not present in the spleen suggesting a role
for soluble factors. MAPC cells suppressed lymphopenia-induced cytokine production in
a prostaglandin E2-dependent manner. This study suggests that MAPC cell therapy may
be useful as a novel strategy to target lymphopenia-induced pathogenic T cell responses
in lymphodepleted patients.
Item Type: | Article |
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Keywords: | multipotent adult progenitor cells; mesenchymal stromal cells; homeostatic proliferation; IL-7; antithymocyte globulin; prostaglandin E2; |
Academic Unit: | Faculty of Science and Engineering > Biology |
Item ID: | 10576 |
Identification Number: | 10.3389/fimmu.2018.00645 |
Depositing User: | Karen English |
Date Deposited: | 25 Feb 2019 10:52 |
Journal or Publication Title: | Frontiers in Immunology |
Publisher: | Frontiers Media |
Refereed: | Yes |
Related URLs: | |
URI: | https://mural.maynoothuniversity.ie/id/eprint/10576 |
Use Licence: | This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here |
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