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Multipotent Adult Progenitor Cells suppress homeostatic driven activation of T cells in vivo

Carty, Fiona ; Corbett, Jennifer M ; da Cunha, Joao Paulo LU orcid ; Reading, James L ; Tree, Timothy I M ; Ting, Anthony E ; Stubblefield, Samantha R and English, Karen (2018) In Cytotherapy 20(5 Suppl 1). p.107-107
Abstract
In the setting of transplantation, T cells are deliberately depleted to prevent allograft rejection. However, this IL-7 activates the accelerated proliferation of effector memory T cells, which are the predominant mediators of graft rejection. Multipotent adult progenitor cells (MAPC) have been previously shown to modulate the response of T cells to IL-7, in vitro but not in vivo. Here, for the first time, we demonstrate that MAPC suppress IL-7 and anti-thymocyte (ATG) driven pro-inflammatory cytokine production by both CD4+ and CD8+ T cells in the spleen. While, MAPC significantly suppressed T cell proliferation in the IL-7 driven model, MAPC did not suppress T cell proliferation in the ATG model when administered on day 4. The effects of... (More)
In the setting of transplantation, T cells are deliberately depleted to prevent allograft rejection. However, this IL-7 activates the accelerated proliferation of effector memory T cells, which are the predominant mediators of graft rejection. Multipotent adult progenitor cells (MAPC) have been previously shown to modulate the response of T cells to IL-7, in vitro but not in vivo. Here, for the first time, we demonstrate that MAPC suppress IL-7 and anti-thymocyte (ATG) driven pro-inflammatory cytokine production by both CD4+ and CD8+ T cells in the spleen. While, MAPC significantly suppressed T cell proliferation in the IL-7 driven model, MAPC did not suppress T cell proliferation in the ATG model when administered on day 4. The effects of routes of administration on the bio-distribution of MAPC in our model of homeostatic proliferation was further clarified using novel 3D whole animal Cryo-imaging technology. MAPC administered i.v. were observed in the spleen 48 hours post injection. However, following i.p. administration, MAPC do not gain access to the spleen but reside in the omentum tissue suggesting that MAPC mediate their effects in the spleen through trophic signalling. Importantly, we demonstrate that MAPC mediate their suppression of pro-inflammatory cytokine production in a PGE-2 dependent manner. Given the importance of successful reconstitution of the immune cell compartment to provide a functional immune system, the fact that MAPC do not suppress this reconstitution but dampen pathogenic cytokine production is a very positive finding. Together this data supports the idea that MAPC may be useful in controlling immune dysregulation via suppression of T cell cytokine production while sparing T cell reconstitution in lymphodepleted patients. (Less)
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author
; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
in
Cytotherapy
volume
20
issue
5 Suppl 1
pages
107 - 107
publisher
Taylor & Francis
ISSN
1477-2566
DOI
10.1016/j.jcyt.2018.02.313
language
English
LU publication?
no
id
3100a420-37dc-4dc8-b343-0afcd398cdf5
date added to LUP
2020-01-30 15:10:05
date last changed
2020-11-12 02:36:48
@misc{3100a420-37dc-4dc8-b343-0afcd398cdf5,
  abstract     = {{In the setting of transplantation, T cells are deliberately depleted to prevent allograft rejection. However, this IL-7 activates the accelerated proliferation of effector memory T cells, which are the predominant mediators of graft rejection. Multipotent adult progenitor cells (MAPC) have been previously shown to modulate the response of T cells to IL-7, in vitro but not in vivo. Here, for the first time, we demonstrate that MAPC suppress IL-7 and anti-thymocyte (ATG) driven pro-inflammatory cytokine production by both CD4+ and CD8+ T cells in the spleen. While, MAPC significantly suppressed T cell proliferation in the IL-7 driven model, MAPC did not suppress T cell proliferation in the ATG model when administered on day 4. The effects of routes of administration on the bio-distribution of MAPC in our model of homeostatic proliferation was further clarified using novel 3D whole animal Cryo-imaging technology. MAPC administered i.v. were observed in the spleen 48 hours post injection. However, following i.p. administration, MAPC do not gain access to the spleen but reside in the omentum tissue suggesting that MAPC mediate their effects in the spleen through trophic signalling. Importantly, we demonstrate that MAPC mediate their suppression of pro-inflammatory cytokine production in a PGE-2 dependent manner. Given the importance of successful reconstitution of the immune cell compartment to provide a functional immune system, the fact that MAPC do not suppress this reconstitution but dampen pathogenic cytokine production is a very positive finding. Together this data supports the idea that MAPC may be useful in controlling immune dysregulation via suppression of T cell cytokine production while sparing T cell reconstitution in lymphodepleted patients.}},
  author       = {{Carty, Fiona and Corbett, Jennifer M and da Cunha, Joao Paulo and Reading, James L and Tree, Timothy I M and Ting, Anthony E and Stubblefield, Samantha R and English, Karen}},
  issn         = {{1477-2566}},
  language     = {{eng}},
  note         = {{Conference Abstract}},
  number       = {{5 Suppl 1}},
  pages        = {{107--107}},
  publisher    = {{Taylor & Francis}},
  series       = {{Cytotherapy}},
  title        = {{Multipotent Adult Progenitor Cells suppress homeostatic driven activation of T cells in vivo}},
  url          = {{http://dx.doi.org/10.1016/j.jcyt.2018.02.313}},
  doi          = {{10.1016/j.jcyt.2018.02.313}},
  volume       = {{20}},
  year         = {{2018}},
}