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Diabetologia
Published in: Diabetologia 4/2012

01-04-2012 | Article

Mesenchymal stem cells differentially mediate regulatory T cells and conventional effector T cells to protect fully allogeneic islet grafts in mice

Authors: D. M. Xu, X. F. Yu, D. Zhang, M. X. Zhang, J. F. Zhou, P. H. Tan, Y. C. Ding

Published in: Diabetologia | Issue 4/2012

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Abstract

Aims/hypothesis

Limited information is available on the cellular interactions between regulatory T (Treg) cells and mesenchymal stem cells (MSCs). In particular, a direct effect of MSCs on the survival and proliferation of Treg cells has not been demonstrated.

Methods

We investigated the effects of MSCs on effector T (Teff) cells and Treg cells, and the molecular mechanisms involved in the distinct regulation of these two cell populations by MSCs in vivo and in vitro.

Results

We show that MSCs are capable of selectively suppressing Teff cells and fostering the generation of Treg cells. Teff cells, but not Treg cells, fail to respond to IL-2 and undergo profound apoptosis in the presence of MSCs. The differential regulations of these two T cell subsets by MSCs are associated with their distinct expressions of CD25, with MSCs specifically reducing the expression of CD25 on Teff and sparing Treg cells intact. In vivo, the administration of MSCs significantly delays the rejection of allogeneic islet grafts in adaptive transferred recipients by favouring the induction of Treg cells. In this model, MSCs inhibit the proliferation and development of alloreactive Teff but potently enhance the induction of Treg cells.

Conclusions/interpretation

We demonstrate that MSCs are capable of regulating Teff and Treg cells differentially in vitro. MSCs inhibit Teff cells by inducing apoptosis and impairing the proliferative response to IL-2 in Teff cells, but favour the survival and expansion of Treg cells. This result is further demonstrated in mice that have undergone allogeneic islet transplantation, in which MSCs suppress alloreactive Teff cells while favouring the induction of Treg cells, thus protecting the islet allografts from rejection.
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Metadata
Title
Mesenchymal stem cells differentially mediate regulatory T cells and conventional effector T cells to protect fully allogeneic islet grafts in mice
Authors
D. M. Xu
X. F. Yu
D. Zhang
M. X. Zhang
J. F. Zhou
P. H. Tan
Y. C. Ding
Publication date
01-04-2012
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 4/2012
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-011-2433-9

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