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Diabetologia

Erschienen in:

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

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

Erschienen in: Diabetologia | Ausgabe 4/2012

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Abstract

Aims/hypothesis

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

Methods

We investigated the effects of MSCs on effector T (T_eff) cells and T_reg 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 T_eff cells and fostering the generation of T_reg cells. T_eff cells, but not T_reg 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 T_eff and sparing T_reg 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 T_reg cells. In this model, MSCs inhibit the proliferation and development of alloreactive T_eff but potently enhance the induction of T_reg cells.

Conclusions/interpretation

We demonstrate that MSCs are capable of regulating T_eff and T_reg cells differentially in vitro. MSCs inhibit T_eff cells by inducing apoptosis and impairing the proliferative response to IL-2 in T_eff cells, but favour the survival and expansion of T_reg cells. This result is further demonstrated in mice that have undergone allogeneic islet transplantation, in which MSCs suppress alloreactive T_eff cells while favouring the induction of T_reg cells, thus protecting the islet allografts from rejection.

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Titel: Mesenchymal stem cells differentially mediate regulatory T cells and conventional effector T cells to protect fully allogeneic islet grafts in mice
verfasst von: D. M. Xu
X. F. Yu
D. Zhang
M. X. Zhang
J. F. Zhou
P. H. Tan
Y. C. Ding
Publikationsdatum: 01.04.2012
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 4/2012
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-011-2433-9

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